lncRNAs in NF-κB-Mediated Macrophage Inflammation: Comparison
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Please note this is a comparison between Version 2 by Jason Zhu and Version 1 by Won-Ha Lee.

Molecular biology’s focus has transitioned from proteins to DNA, and now to RNA. Once considered merely a genetic information carrier, RNA is now recognized as both a vital element in early cellular life and a regulator in complex organisms. Long noncoding RNAs (lncRNAs), which are over 200 bases long but do not code for proteins, play roles in gene expression regulation and signal transduction by inducing epigenetic changes or interacting with various proteins and RNAs. These interactions exhibit a range of functions in various cell types, including macrophages. Notably, some macrophage lncRNAs influence the activation of NF-κB, a crucial transcription factor governing immune and inflammatory responses. Macrophage NF-κB is instrumental in the progression of various pathological conditions including sepsis, atherosclerosis, cancer, autoimmune disorders, and hypersensitivity.

  • human diseases
  • inflammation
  • lncRNA
  • macrophage
  • NF-κB

1. LncRNAs That Modulate Macrophage NF-κB Activity in Sepsis

Sepsis is a life-threatening condition marked by a dysregulated immune response to infection, leading to widespread inflammation, organ dysfunction, and potentially organ failure and death [28][1]. Often caused by bacteria, viruses, fungi, or other pathogens, a prime stimulant is LPS, an endotoxin found in the cell wall of Gram-negative bacteria [29][2]. The systemic inflammatory response, particularly post-bloodstream infection, triggers an excessive release of pro-inflammatory cytokines and chemokines. These mediators damage the endothelial cells lining the walls of blood vessels, resulting in increased permeability. This, in turn, leads to fluid leakage, tissue swelling, and subsequently edema [30][3]. Persistent inflammation can impact multiple organs and systems, with cytokines like TNF-α being key mediators of sepsis [31][4]. Commonly affected organs include the lungs, heart, kidneys, liver, and even the central nervous system.
NF-κB-mediated inflammation in macrophages, followed by M1 polarization, is pivotal in the pathogenesis of sepsis [32][5]. Pattern recognition receptors, including Toll-like receptors (TLRs), allow macrophages to identify pathogen-associated molecular patterns on invading microorganisms [29][2]. Activation of NF-κB, triggered by LPS interaction with TLR4 via the canonical pathway, upregulates numerous pro-inflammatory genes, such as cytokines, chemokines, adhesion molecules, and enzymes like inducible nitric oxide synthase [33][6]. NF-κB serves as a primary target for immunomodulatory therapies aimed at regulating inflammation and reestablishing immune equilibrium in many diseases, including sepsis. Such strategies might involve inhibiting NF-κB activation or employing targeted therapies to neutralize specific pro-inflammatory cytokines.
The lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1), confined to the nucleus, is instrumental in forming paraspeckles, subnuclear structures involved in antiviral responses [34][7]. The levels of NEAT1 are increased by more than two-fold in the sera of sepsis patients [35,36,37,38][8][9][10][11]. Induced by LPS in the human monocytic leukemia cell line THP-1, NEAT1 enhances inflammatory responses by sponging miR-17-5p, thereby stabilizing TLR4 mRNA (the miR-17-5p/TLR4 axis) [38][11]. In Kupffer cells and the murine macrophages, LPS-induced NEAT1 promotes inflammatory activities via the Let-7q/TLR4 axis [35,36,37,39][8][9][10][12]. Additionally, NEAT1 also facilitates M1 polarization in macrophages through the miR-125a-5p/TRAF6/TGF-β-activated kinase 1 (TAK1) axis [40][13], underscoring its potential as a therapeutic target for sepsis.
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a multifunctional lncRNAs in macrophages, is extensively studied. In late-onset sepsis patients, increased blood MALAT1 levels correlate with disease severity [41][14]. The expression of MALAT1 increases in activated macrophages, exhibiting an elevation greater than two-fold in mouse peripheral blood mononuclear cells (PBMCs) and more than six-fold in THP-1-derived macrophages, especially following LPS treatment [41,42][14][15]. Animal studies show that MALAT1 expression surges with sepsis induction; reducing MALAT1 lessens inflammation and mortality [41,43[14][16][17][18],44,45], possibly by suppressing M1 and enhancing M2 macrophage polarization [45][18]. In an LPS-induced septic lung injury model, intravenous MALAT1-specific small interfering RNA (siRNA) decreases inflammatory cytokines and immune cells in bronchoalveolar lavage fluid by inhibiting the p38 mitogen-activated protein kinase (MAPK)/p65 pathway [44][17].
However, several reports have shown contradictory evidence, indicating a significant decrease in MALAT1 expression accompanied by an increase in hsa-miR-346 levels in patients with sepsis. Activated human and mouse macrophages downregulate MALAT1 expression in an NF-κB-dependent manner [42,46][15][19]. MALAT1 interacts with NF-κB, inhibiting its DNA-binding activity and, consequently, the expression of pro-inflammatory cytokines [42][15]. Furthermore, MALAT1 modulates macrophage proliferation by sequestering hsa-miR-346, thereby stabilizing the mRNA of small mothers against decapentaplegic homolog 3 (SMAD3). SMAD3 is a receptor-regulated signaling adaptor that is activated by serine kinases. These conflicting findings underscore the need for future research on MALAT1’s role in sepsis.
In sepsis patients, the levels of long noncoding RNA plasmacytoma variant translocation 1 (PVT1) are elevated, showing an increase of more than two-fold compared to the healthy control group. This elevation correlates with increased pro-inflammatory mediators and survival rates. [47,48][20][21]. LPS induces PVT1 expression in THP-1 cells, which in turn amplifies NF-κB activity via p38 stimulation [49][22]. Elevated PVT1 expression, promoting M1 polarization through the miR-29a/high-mobility group box 1 (HMGB1) axis, is observed in heart-infiltrating macrophages of septic mice [50][23]. HMGB1, released from the cells, can activate TLR4 in both autocrine and paracrine manners [51][24]. PVT1 is also highly expressed in osteoarthritis patients’ serum and in the LPS-stimulated C28/12 chondrocyte cell line, activating the TLR4/NF-κB pathway via the miR-93-5p/HMGB1 axis [52][25]. Additionally, PVT1 levels rise in myocardial tissues and heart-infiltrating macrophages during sepsis-induced myocardial injury [50][23].
The expression level of lncRNA MEG3 is significantly reduced in patients with sepsis, and this reduction has prognostic significance [53][26]. In macrophages, MEG3 overexpression inhibits LPS-induced apoptosis by downregulating BAX and upregulating Bcl-2. It also suppresses inflammatory factor expression by inhibiting NF-κB signaling [53][26]. This suggests that the reduced MEG3 expression may exacerbate sepsis by increasing inflammation and inhibiting apoptosis in macrophages. Further research is needed to elucidate MEG3’s role in sepsis.
In sepsis patients, the lncRNA colorectal neoplasia differentially expressed (CRNDE) exhibits elevated expression in peripheral blood, with higher levels correlating to improved survival rates [54][27]. CRNDE intensifies LPS-induced NF-κB activation and subsequent pro-inflammatory cytokine release in THP-1 cells via the miR-181-5p/TLR4 axis [54][27].
These reports highlight the intricate relationship between lncRNAs and NF-κB in the context of sepsis, impacting inflammatory activation and macrophage polarization. The influence of these lncRNAs on cytokine release, cell polarization, and apoptosis is notable, and their varied expression in sepsis patients suggests potential as biomarkers. Targeting these lncRNAs to regulate NF-κB activation offers promising avenues for immunomodulatory therapies to manage inflammation and restore immune balance in sepsis. However, the contrasting roles of specific lncRNAs, like MALAT1, necessitate further research. A deeper understanding of these lncRNAs’ roles could lead to innovative diagnostic and therapeutic strategies, improving management and outcomes in sepsis.

2. LncRNAs That Modulate Macrophage NF-κB Activity in Atherosclerosis

Macrophages are central in atherosclerosis development, marked by arterial plaque build-up. The process initiates with low-density lipoprotein (LDL) cholesterol accumulation in arterial walls, undergoing oxidation and eliciting inflammation [55,56][28][29]. Modified LDL attracts monocytes from blood, transforming into macrophages in the arterial wall. These macrophages consume oxidized LDL (oxLDL), forming lipid-laden foam cells and creating fatty streaks, early atherosclerosis signs [57,58][30][31]. M1 macrophages exacerbate inflammation by releasing cytokines, attracting more immune cells [59,60][32][33]. Chronic inflammation leads to fibrous cap formation over plaques and extracellular matrix accumulation. Macrophages also degrade this matrix, heightening plaque instability and increasing heart attack and stroke risks [57,61][30][34]. Macrophages can also contribute to the resolution of inflammation and healing processes [62][35]. In atherosclerosis, inflammation resolution is overshadowed by ongoing inflammation and plaque growth.
NF-κB, activated by stimuli such as oxidative stress, cytokines, and oxLDL, exacerbate atherosclerosis by promoting lipoprotein uptake, foam cell formation, and attracting more immune cells [57,63][30][36]. This activation also destabilizes plaques by encouraging matrix metalloproteinase (MMP) secretion, increasing plaque rupture risks [64][37]. Chronic NF-κB activation sustains the inflammation characteristics of advanced atherosclerosis in conditions like coronary artery diseases (CADs) and myocardial infarction (MI) [65][38]. Given its crucial role in macrophage activation atherosclerosis progression, NF-κB presents a potential target for therapies aimed at reducing inflammation and slowing atherosclerosis progression [66][39].
Increased NEAT1 expression levels in the PBMCs and sera of atherosclerosis patients have been noted [67,68][40][41]. The expression level of NEAT1 was found to be increased by more than two-fold in PBMCs of CAD patients [67][40]. NEAT1, induced by oxLDL in THP-1 cells, contributes to pro-inflammatory responses by enhancing p65 phosphorylation, followed by paraspeckle formation [69,70][42][43]. It is also induced in bone marrow-derived macrophages (BMDMs) treated with titanium particles and promotes NF-κB activation, NLRP3 inflammasome formation, and M1 polarization via the miR-188-5p/Bruton’s tyrosine kinase (BTK) axis [71][44]. NEAT1 also stimulates pro-inflammatory cytokine and reactive oxygen species (ROS) production and subsequent foam cell formation by sponging miR-342-3p in THP-1 cells [70][43] or miR-128 in the murine macrophage-like cell line RAW264.7 [72][45]. These reports agree with NEAT1 being expressed in activated macrophages and enhancing pro-inflammatory changes. One contradicting study, however, reported decreased NEAT1 in the PBMCs of post-MI patients and enhanced macrophage inflammation in NEAT1-knockout mice [73][46].
Elevated lncRNA PVT1 levels have been detected in the serum of atherosclerosis patients [74][47]. Inhibiting PVT1 in animal models reduces atherosclerotic plaques by increasing HDL levels and suppressing the MAPK/NF-κB pathway and pro-atherogenic factors [74][47]. In serum samples of atherosclerosis patients and during oxLDL-induced THP-1 cell foam cell differentiation, there is a notable increase in lncRNA small nucleolar RNA host gene (SNHG)16 and a decrease in miR-17-5p [75][48]. SNHG16 amplifies macrophage proliferation and pro-inflammatory responses in atherosclerosis through the miR-17-5p/NF-κB axis [75][48].
LncRNA X-inactive specific transcript (XIST), known for its role in X-chromosome inactivation, has been found to be elevated more than two-fold in the serum of atherosclerosis patients, oxLDL-treated vascular smooth muscle cells, and the U937 human monocytic leukemia cell line [76][49]. XIST influences atherosclerosis by promoting proliferation and inhibiting apoptotic cell death through the miR-599/TLR4 axis [76][49]. This finding aligns with other studies that show that apoptosis inhibition aggravates atherogenesis by increasing macrophage proliferation and plaque formation [77,78][50][51].
LncRNA H19 is found at elevated levels in the serum of atherosclerosis patients [79,80,81,82][52][53][54][55]. OxLDL stimulates H19 expression in macrophages [83][56], aorta vascular smooth muscle cells [79[52][53],80], and human umbilical vein endothelial cells (HUVECs) [84][57]. In macrophages, H19 augments oxLDL-induced lipid accumulation, ROS generation, and NF-κB activation [83,85][56][58]. Similarly, in HUVECs, H19 heightens NF-κB activation by increasing p38 and p65 activity [86][59]. These findings suggest that H19 could be a promising therapeutic target for atherosclerosis treatment.
In atherosclerosis and CAD patients, MALAT1 levels rise more than two-fold and subsequently fall after treatment [87,88,89][60][61][62]. MALAT1 impacts various macrophage processes like foam cell formation, autophagy, and pyroptosis [90,91,92][63][64][65]. OxLDL prompts NF-κB-dependent MALAT1 expression in THP-1 cells. MALAT1 then enhances lipid uptake and foam cell formation by promoting scavenger receptor CD36 expression [88,90,91][61][63][64]. MALAT1 also enhances NF-κB activation and subsequent inflammation by sponging miR-330-5p [91][64]. Further, oxLDL-induced autophagy in macrophage is mediated by MALAT1, which activates the MAPK/NF-κB pathway and inhibits sirtuin 1 (SIRT1), a key transcription factor deacetylase [92,93][65][66]. NLRP3 inflammasome-mediated pyroptosis, a programmed cell death as a defense mechanism against intracellular pathogens, is also influenced by MALAT1 [94][67]. In diabetic atherosclerosis models, a cinnamic acid derivative reduces inflammasome activation and pyroptosis by suppressing MALAT1 [95][68]. Extracellular vesicles (EVs) such as exosomes are crucial for cell-to-cell communication, transferring proteins and lncRNAs [96][69]. M1 macrophages have been found to release MALAT1-containing EVs, which regulate myocyte proliferation and angiogenesis in MI models [97][70]. These findings underscore MALAT1’s role in atherosclerosis: it is upregulated in activated macrophages and influences various processes including lipid uptake, foam cell formation, and cell death.
However, contrary reports exist regarding the role of MALAT1 in atherosclerosis. It was observed that in atherosclerosis patients and oxLDL-treated THP-1 cells, MALAT1 levels decrease [88][61]. Reduced MALAT1 leads to increased lipid and total cholesterol accumulation in THP-1 cells via the miR-17-5p/ATP-binding cassette subfamily A member 1 (ABCA1) axis [88][61]. ABCA1 is known to facilitate cholesterol efflux, thereby reducing foam cell formation [98][71]. Additionally, MALAT1 deficiency in certain mouse models has been linked to accelerated macrophage inflammation and atherosclerosis [99][72]. Exosomal MALAT1 from oxLDL-treated HUVECs promotes a transition from M1 to M2 macrophages [100][73]. These findings suggest potential anti-atherogenic properties of MALAT1, highlighting the need for further research to clarify its role in atherosclerosis.
Notably, the expression levels of lncRNA HOX transcript antisense intergenic RNA (HOTAIR) are decreased in the peripheral blood lymphocytes of atherosclerosis patients and oxLDL-treated RAW264.7 cells [101][74]. HOTAIR overexpression reduces pro-inflammatory cytokine expression while boosting anti-inflammatory cytokines, achieved by inhibiting NF-κB activity. This suppression occurs through HOTAIR’s enhancement of fragile X-related protein 1 (FXR1) levels, a protein moving between the nucleus and cytoplasm and associating with polyribosomes [101,102][74][75].
These reports underscore the complex relationship between various lncRNAs and macrophage NF-κB in atherosclerosis. These lncRNAs impact crucial aspects such as lipid uptake, foam cell formation, inflammation, and cell death in macrophages. Given their link to NF-κB activation, targeting these lncRNAs for NF-κB modulation presents a promising approach to managing atherosclerosis by restoring immune equilibrium and curbing inflammatory activation. It is intriguing that certain lncRNAs, such as MALAT1 and HOTAIR, have been identified to play conflicting roles in atherosclerosis. Variations in the stages of atherosclerosis or CAD examined, the measurement techniques utilized, environmental factors, or the experimental model systems employed could account for these discrepancies. Alternatively, the overall impact of these lncRNAs may differ based on the dominant signaling pathways activated in particular contexts or disease states. Despite the conflict, their significant influence on macrophage function and disease progression is evident. Further research is essential to unravel the full potential of these lncRNAs in atherosclerosis treatment.

3. LncRNAs That Modulate Macrophage NF-κB Activity in Cancer

The role of macrophage inflammation in cancer is multifaceted and contradictory. M1 macrophages, typically anti-tumorigenic, can attack tumor cells and stimulate immune responses. Conversely, M2 macrophages often aid tumor growth by supporting angiogenesis, suppressing immune responses, and facilitating tissue remodeling [125][76]. Generally, tumor-associated macrophages (TAMs) exhibit an M2 phenotype, supporting tumor growth and metastasis and contributing to an immunosuppressive tumor environment [126,127][77][78]. Given their significant impact on cancer progression, TAMs are being investigated as therapeutic targets, with strategies focusing on inhibiting their tumor-promoting functions or reprogramming them to combat tumors.
The activation of NF-κB in macrophages plays a crucial role in cancer development and progression. In TAMs, NF-κB activation leads to the production of cytokines, growth factors, and enzymes that promote tumor growth and suppress anti-tumor immune responses [128,129][79][80]. NF-κB can also alter the immune microenvironment, potentially inducing immune checkpoint molecules that weaken the immune response against tumors [130][81]. Additionally, NF-κB-activated macrophages can produce angiogenic factors, aiding tumor vascularization [131,132,133][82][83][84]. They can also stimulate matrix metalloproteinases (MMPs), breaking down extracellular matrix barriers and facilitating cancer cell spread [134,135][85][86]. Thus, macrophage NF-κB is implicated in various aspects of cancer progression and targeting macrophage NF-κB has emerged as a prominent focus in cancer treatment strategies [18][87].
LncRNA DC-STAMP domain containing 1-antisense 1 (DCST1-AS1) has been investigated in various cancers, including gastric, colorectal, cervical, breast, glioblastoma, endometrial, and HCC [136,137,138,139,140,141,142][88][89][90][91][92][93][94]. In these cancers, increased DCST1-AS1 expression correlates with larger tumors and shorter survival and DCST1-AS1 promotes cancer cell proliferation and metastasis, and inhibits apoptosis, by sponging miRNAs [136,137,138,139,140,141,142][88][89][90][91][92][93][94]. Notably, in oral squamous cell carcinoma, DCST1-AS1 advances tumor progression by enhancing NF-κB activity in cancer cells and macrophages [115][95]. The expression of DCST1-AS1 showed a more than three-fold increase in oral squamous cell carcinoma cells compared to normal cells [115][95]. Elevated DCST1-AS1 in cancer cells and M2 macrophages is linked to tumor growth and cancer cell proliferation. NF-κB antagonists revealed that DCST1-AS1 enhances cancer progression and M2 macrophage polarization through NF-κB-mediated mechanisms [115][95].
The lncRNA FGD5 antisense RNA 1 (FGD5-AS1) shows elevated levels in non-small-cell lung cancer and pancreatic cancer, correlating with metastasis and poor prognosis [120,143][96][97]. FGD5-AS1-containing exosomes from these cancers induce M2 macrophage polarization [120][96]. FGD5-AS1 links acetyltransferase p300, STAT3, and NF-κB, leading to acetylated STAT3/p65 complex and transcriptional activation [120,144][96][98]. STATs are crucial transcription factors in macrophage polarization, with STAT1 being integral to M1, and STAT3/6 to M2 polarization. [145][99]. In cervical cancer, FGD5-AS1, via the miR-129-5p/bone marrow stromal cell antigen 2 (BST2) axis, promotes tumor growth and M2 polarization [146][100]. BST2, a lipid raft-associated protein, is implicated in cell proliferation and immune response [147,148][101][102]. Collectively, FGD5-AS1 augments tumor growth by enhancing cancer progression and M2 macrophage polarization.
The lncRNA AP000439.2 has recently been identified as a prognostic marker for renal cell carcinoma (RCC) patient survival [149,150][103][104]. Exosomes from human RCC cell lines have been shown to induce M2 polarization in co-cultured THP-1 cells [121][105]. AP000439.2 promotes M2 polarization through the phosphorylation of STAT3 and the NF-κB p65 subunit, which, in turn, enhances the migration potential of cocultured cancer cell lines. The impact of exosomal AP000439.2 on macrophage M2 polarization and RCC growth has been confirmed in a xenograft tumor mouse model [121][105].
LncRNA Five Prime to Xist (FTX), an evolutionarily conserved regulator of XIST expression, is associated with various conditions including malignancies, endometriosis, and stroke, functioning through miRNA sponging [151,152][106][107]. Liu et al. observed decreased FTX levels in cirrhosis patients, linking them to abnormal activation of CD14+ CD16+ monocytes via the miR-545/T cell immunoglobulin and mucin domain 3 (Tim-3) axis [116,153][108][109]. Moreover, FTX suppression in THP-1 cells increases NF-κB activity and pro-inflammatory cytokine expression, suggesting that a reduction in FTX might accelerate tumor progression by enhancing inflammation in the tumor microenvironment (TME) [116][108].
LncRNA HOTAIR, known for its role in gene regulation and epigenetic modifications, is implicated in various human diseases [154][110]. It is often overexpressed in cancer, contributing to tumor progression, metastasis, and poor prognosis by altering gene expression related to the cell cycle, apoptosis, and metastasis [154,155][110][111]. HOTAIR is also associated with central nervous system disorders, fibrosis, and inflammatory conditions, impacting cellular processes and immune responses [156,157,158,159][112][113][114][115]. It regulates glucose transporter isoform 1 (GLUT1) expression in human neuroblastoma cells and macrophages by stimulating NF-κB activity, suggesting a role in metabolic reprogramming in cancer [117,160][116][117]. In addition, inflammatory activation of macrophages triggers HOTAIR expression, which then promotes NF-κB activation and cytokine gene expression by aiding in the degradation of IκBα [117][116]. HOTAIR’s expression pattern in cancer tissue macrophages remains unexplored and warrants future investigation.
Elevated levels of lncRNA HOXA transcript at the distal tip (HOTTIP) have been observed in AML patients and cell lines, such as U937 and THP-1 [161][118]. HOTTIP facilitates cell proliferation via the miR-608/DET1- and DDB1-associated 1 (DDA1) axis, with DDA1 being a gene known for its oncogenic properties [161,162][118][119]. In squamous cell carcinoma, M1-derived exosomes containing HOTTIP inhibit cancer cell proliferation and induce apoptosis by activating the TLR5/NF-κB pathway [123][120]. Additionally, exosomal HOTTIP influences the M1 polarization of circulating monocytes [123][120]. The comprehensive role of HOTTIP in cancer progression remains an area for future exploration.
Cyclooxygenase (COX)2, linked with inflammation in immune cells, is implicated in several cancers [163][121]. LncRNA p50-associated COX2 extragenic RNA (PACER), located upstream of the COX2 promoter, regulates COX2 expression [106][122]. PACER, through its association with p50, facilitates p65/p50 heterodimer binding to the COX2 promoter, recruiting p300 histone acetyltransferase [106][122]. Its expression is upregulated in various cancer tissues, influencing COX2 and PGE2 synthesis and cancer cell proliferation, migration, and invasion [164,165,166][123][124][125].
LncRNA cardiac hypertrophy-related factor (CHRF) functions as an oncogene, promoting migration and invasion in various tumor types [167][126]. In a silica-induced pulmonary fibrosis mouse model, CHRF activates inflammatory and fibrotic pathways via the miR-489/MyD88 and miR-489/SMAD3 axes, with SMAD3 being an adaptor in receptor-regulated signaling [108,168][127][128]. CHRF’s pro-inflammatory effects are also observed in LPS-induced acute lung injury [169][129]. However, its specific role in macrophage inflammation within the TME remains unclear, necessitating further research.
LncRNA SNHG1, commonly overexpressed in various cancers as an oncogene, affects cellular signaling via interactions with miRNAs and signaling regulators [170][130]. In cholangiocarcinoma cell lines, SNHG1 is associated with increased proliferation and invasion, mediated by NF-κB activation through the miR-140/TLR4 axis, contributing to an inflammatory TME [171][131]. In an LPS-induced acute lung injury model, SNHG1 is upregulated in M1 polarized THP-1 cells, enhancing NF-κB activation and inflammation through interaction with HMGB1 [114][132]. However, SNHG1’s specific role in macrophage-related TME remains unexplored.
These findings highlight the intricate relationship between macrophages, lncRNAs, and NF-κB in cancer, affecting cell proliferation, invasion, inflammation, and macrophage polarization. The dichotomy of macrophages, especially TAMs, underscores their potential as therapeutic targets. Their influence extends to inflammation, TME modulation, angiogenesis, and immunosuppression, making them key in the interplay between cancer cells and the immune system. Understanding lncRNA-driven macrophage NF-κB regulation is essential for developing targeted cancer therapies. Despite advances, many aspects of lncRNA functions in cancer and inflammation require further exploration, presenting exciting opportunities for future research and potential therapeutic interventions.

References

  1. Pravda, J. Sepsis: Evidence-based pathogenesis and treatment. World J. Crit. Care Med. 2021, 10, 66–80.
  2. Cristofaro, P.; Opal, S.M. The Toll-like receptors and their role in septic shock. Expert. Opin. Ther. Targets 2003, 7, 603–612.
  3. Chousterman, B.G.; Swirski, F.K.; Weber, G.F. Cytokine storm and sepsis disease pathogenesis. Semin. Immunopathol. 2017, 39, 517–528.
  4. Tracey, K.J.; Beutler, B.; Lowry, S.F.; Merryweather, J.; Wolpe, S.; Milsark, I.W.; Hariri, R.J.; Fahey, T.J., 3rd; Zentella, A.; Albert, J.D.; et al. Shock and tissue injury induced by recombinant human cachectin. Science 1986, 234, 470–474.
  5. Chen, X.; Liu, Y.; Gao, Y.; Shou, S.; Chai, Y. The roles of macrophage polarization in the host immune response to sepsis. Int. Immunopharmacol. 2021, 96, 107791.
  6. Liu, S.F.; Malik, A.B. NF-kappa B activation as a pathological mechanism of septic shock and inflammation. Am. J. Physiol. Lung Cell Mol. Physiol. 2006, 290, L622–L645.
  7. Naganuma, T.; Nakagawa, S.; Tanigawa, A.; Sasaki, Y.F.; Goshima, N.; Hirose, T. Alternative 3’-end processing of long noncoding RNA initiates construction of nuclear paraspeckles. EMBO J. 2012, 31, 4020–4034.
  8. Zhang, C.C.; Niu, F. LncRNA NEAT1 promotes inflammatory response in sepsis-induced liver injury via the Let-7a/TLR4 axis. Int. Immunopharmacol. 2019, 75, 105731.
  9. Xia, D.; Yao, R.; Zhou, P.; Wang, C.; Xia, Y.; Xu, S. LncRNA NEAT1 reversed the hindering effects of miR-495-3p/STAT3 axis and miR-211/PI3K/AKT axis on sepsis-relevant inflammation. Mol. Immunol. 2020, 117, 168–179.
  10. Wu, X.Y.; Fang, Y.; Zheng, F.X.; Zhang, Y.Z.; Li, Q.L. LncRNA NEAT1 facilitates the progression of sepsis through up-regulating TSP-1 via sponging miR-370-3p. Eur. Rev. Med. Pharmacol. Sci. 2020, 24, 333–344.
  11. Li, Y.; Guo, W.; Cai, Y. NEAT1 Promotes LPS-induced Inflammatory Injury in Macrophages by Regulating MiR-17-5p/TLR4. Open Med. 2020, 15, 38–49.
  12. Yang, Y.; Xue, J.; Qin, L.; Zhang, J.; Liu, J.; Yu, J. LncRNA NEAT1 Promotes Inflammatory Response in Sepsis via the miR-31-5p/POU2F1 Axis. Inflammation 2021, 44, 1518–1528.
  13. Wang, W.; Guo, Z.H. Downregulation of lncRNA NEAT1 Ameliorates LPS-Induced Inflammatory Responses by Promoting Macrophage M2 Polarization via miR-125a-5p/TRAF6/TAK1 Axis. Inflammation 2020, 43, 1548–1560.
  14. Chen, J.; Tang, S.; Ke, S.; Cai, J.J.; Osorio, D.; Golovko, A.; Morpurgo, B.; Guo, S.; Sun, Y.; Winkle, M.; et al. Ablation of long noncoding RNA MALAT1 activates antioxidant pathway and alleviates sepsis in mice. Redox Biol. 2022, 54, 102377.
  15. Zhao, G.; Su, Z.; Song, D.; Mao, Y.; Mao, X. The long noncoding RNA MALAT1 regulates the lipopolysaccharide-induced inflammatory response through its interaction with NF-kappaB. FEBS Lett. 2016, 590, 2884–2895.
  16. Dai, L.; Zhang, G.; Cheng, Z.; Wang, X.; Jia, L.; Jing, X.; Wang, H.; Zhang, R.; Liu, M.; Jiang, T.; et al. Knockdown of LncRNA MALAT1 contributes to the suppression of inflammatory responses by up-regulating miR-146a in LPS-induced acute lung injury. Connect. Tissue Res. 2018, 59, 581–592.
  17. Lin, L.P.; Niu, G.H.; Zhang, X.Q. Influence of lncRNA MALAT1 on septic lung injury in mice through p38 MAPK/p65 NF-kappaB pathway. Eur. Rev. Med. Pharmacol. Sci. 2019, 23, 1296–1304.
  18. Cui, H.; Banerjee, S.; Guo, S.; Xie, N.; Ge, J.; Jiang, D.; Zornig, M.; Thannickal, V.J.; Liu, G. Long noncoding RNA Malat1 regulates differential activation of macrophages and response to lung injury. JCI Insight. 2019, 4, 124522.
  19. Yang, Q.; Cao, K.; Jin, G.; Zhang, J. Hsa-miR-346 plays a role in the development of sepsis by downregulating SMAD3 expression and is negatively regulated by lncRNA MALAT1. Mol. Cell Probes 2019, 47, 101444.
  20. Chen, J.; Ren, H.; Liu, B. Evaluating the potency of blood long noncoding RNA PVT1 as candidate biomarker reflecting inflammation, multiple organ dysfunction, and mortality risk in sepsis patients. J. Clin. Lab. Anal. 2022, 36, e24268.
  21. Yuan, W.; Xiong, X.; Du, J.; Fan, Q.; Wang, R.; Zhang, X. LncRNA PVT1 accelerates LPS-induced septic acute kidney injury through targeting miR-17-5p and regulating NF-kappaB pathway. Int. Urol. Nephrol. 2021, 53, 2409–2419.
  22. Zheng, S.; Li, W.; Liao, W.; Huang, C.; Zhou, M.; Zheng, Y.; Zou, Z.; He, Z. Silencing of LncRNA-PVT1 ameliorates lipopolysaccharide-induced inflammation in THP-1-derived macrophages via inhibition of the p38 MAPK signaling pathway. Ann. Palliat. Med. 2021, 10, 6410–6418.
  23. Luo, Y.Y.; Yang, Z.Q.; Lin, X.F.; Zhao, F.L.; Tu, H.T.; Wang, L.J.; Wen, M.Y.; Xian, S.X. Knockdown of lncRNA PVT1 attenuated macrophage M1 polarization and relieved sepsis induced myocardial injury via miR-29a/HMGB1 axis. Cytokine 2021, 143, 155509.
  24. Hreggvidsdottir, H.S.; Lundberg, A.M.; Aveberger, A.C.; Klevenvall, L.; Andersson, U.; Harris, H.E. High mobility group box protein 1 (HMGB1)-partner molecule complexes enhance cytokine production by signaling through the partner molecule receptor. Mol. Med. 2012, 18, 224–230.
  25. Meng, Y.; Qiu, S.; Sun, L.; Zuo, J. Knockdown of exosome-mediated lnc-PVT1 alleviates lipopolysaccharide-induced osteoarthritis progression by mediating the HMGB1/TLR4/NF-kappaB pathway via miR-93-5p. Mol. Med. Rep. 2020, 22, 5313–5325.
  26. Pan, X.; He, L. LncRNA MEG3 expression in sepsis and its effect on LPS-induced macrophage function. Cell. Mol. Biol. (Noisy-le-grand) 2020, 66, 131–136.
  27. Wang, Y.; Xu, Z.; Yue, D.; Zeng, Z.; Yuan, W.; Xu, K. Linkage of lncRNA CRNDE sponging miR-181a-5p with aggravated inflammation underlying sepsis. Innate Immun. 2020, 26, 152–161.
  28. Gibson, M.S.; Domingues, N.; Vieira, O.V. Lipid and Non-lipid Factors Affecting Macrophage Dysfunction and Inflammation in Atherosclerosis. Front. Physiol. 2018, 9, 654.
  29. Lusis, A.J. Atherosclerosis. Nature 2000, 14, 233–241.
  30. Libby, P. Atherosclerosis in Inflammation. Nature 2002, 420, 868–874.
  31. Ross, R. Atherosclerosis--an inflammatory disease. N. Engl. J. Med. 1999, 340, 115–126.
  32. Wu, J.; He, S.; Song, Z.; Chen, S.; Lin, X.; Sun, H.; Zhou, P.; Peng, Q.; Du, S.; Zheng, S.; et al. Macrophage polarization states in atherosclerosis. Front. Immunol. 2023, 14, 1185587.
  33. Momtazi-Borojeni, A.A.; Abdollahi, E.; Nikfar, B.; Chaichian, S.; Ekhlasi-Hundrieser, M. Curcumin as a potential modulator of M1 and M2 macrophages: New insights in atherosclerosis therapy. Heart Fail. Rev. 2019, 24, 399–409.
  34. Park, S.H. Regulation of Macrophage Activation and Differentiation in Atherosclerosis. J. Lipid Atheroscler. 2021, 10, 251–267.
  35. Tabas, I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat. Rev. Immunol. 2010, 10, 36–46.
  36. Jiang, H.; Zhou, Y.; Nabavi, S.M.; Sahebkar, A.; Little, P.J.; Xu, S.; Weng, J.; Ge, J. Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis. Front. Cardiovasc. Med. 2022, 9, 925923.
  37. Watanabe, N.; Ikeda, U. Matrix metalloproteinases and atherosclerosis. Curr. Atheroscler. Rep. 2004, 6, 112–120.
  38. Wilson, H.M. The intracellular signaling pathways governing macrophage activation and function in human atherosclerosis. Biochem. Soc. Trans. 2022, 50, 1673–1682.
  39. Taghizadeh, E.; Taheri, F.; Renani, P.G.; Reiner, Z.; Navashenaq, J.G.; Sahebkar, A. Macrophage: A Key Therapeutic Target in Atherosclerosis? Curr. Pharm. Des. 2019, 25, 3165–3174.
  40. Vlachogiannis, N.I.; Sachse, M.; Georgiopoulos, G.; Zormpas, E.; Bampatsias, D.; Delialis, D.; Bonini, F.; Galyfos, G.; Sigala, F.; Stamatelopoulos, K.; et al. Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease. J. Mol. Cell Cardiol. 2021, 160, 111–120.
  41. Guo, J.T.; Wang, L.; Yu, H.B. Knockdown of NEAT1 mitigates ox-LDL-induced injury in human umbilical vein endothelial cells via miR-30c-5p/TCF7 axis. Eur. Rev. Med. Pharmacol. Sci. 2020, 24, 9633–9644.
  42. Huang-Fu, N.; Cheng, J.S.; Wang, Y.; Li, Z.W.; Wang, S.H. Neat1 regulates oxidized low-density lipoprotein-induced inflammation and lipid uptake in macrophages via paraspeckle formation. Mol. Med. Rep. 2018, 17, 3092–3098.
  43. Wang, L.; Xia, J.W.; Ke, Z.P.; Zhang, B.H. Blockade of NEAT1 represses inflammation response and lipid uptake via modulating miR-342-3p in human macrophages THP-1 cells. J. Cell Physiol. 2019, 234, 5319–5326.
  44. Lin, S.; Wen, Z.; Li, S.; Chen, Z.; Li, C.; Ouyang, Z.; Lin, C.; Kuang, M.; Xue, C.; Ding, Y. LncRNA Neat1 promotes the macrophage inflammatory response and acts as a therapeutic target in titanium particle-induced osteolysis. Acta Biomater. 2022, 142, 345–360.
  45. Chen, D.D.; Hui, L.L.; Zhang, X.C.; Chang, Q. NEAT1 contributes to ox-LDL-induced inflammation and oxidative stress in macrophages through inhibiting miR-128. J. Cell Biochem. 2018, 120, 2493–2501.
  46. Gast, M.; Rauch, B.H.; Haghikia, A.; Nakagawa, S.; Haas, J.; Stroux, A.; Schmidt, D.; Schumann, P.; Weiss, S.; Jensen, L.; et al. Long noncoding RNA NEAT1 modulates immune cell functions and is suppressed in early onset myocardial infarction patients. Cardiovasc. Res. 2019, 115, 1886–1906.
  47. Du, H.; Zhang, H.; Yang, R.; Qiao, L.; Shao, H.; Zhang, X. Small interfering RNA-induced silencing lncRNA PVT1 inhibits atherosclerosis via inactivating the MAPK/NF-kappaB pathway. Aging 2021, 13, 24449–24463.
  48. An, J.H.; Chen, Z.Y.; Ma, Q.L.; Wang, H.J.; Zhang, J.Q.; Shi, F.W. LncRNA SNHG16 promoted proliferation and inflammatory response of macrophages through miR-17-5p/NF-kappaB signaling pathway in patients with atherosclerosis. Eur. Rev. Med. Pharmacol. Sci. 2019, 23, 8665–8677.
  49. Yang, K.; Xue, Y.; Gao, X. LncRNA XIST Promotes Atherosclerosis by Regulating miR-599/TLR4 Axis. Inflammation 2021, 44, 965–973.
  50. Sun, C.; Fu, Y.; Gu, X.; Xi, X.; Peng, X.; Wang, C.; Sun, Q.; Wang, X.; Qian, F.; Qin, Z.; et al. Macrophage-Enriched lncRNA RAPIA: A Novel Therapeutic Target for Atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2020, 40, 1464–1478.
  51. Gareev, I.; Kudriashov, V.; Sufianov, A.; Begliarzade, S.; Ilyasova, T.; Liang, Y.; Beylerli, O. The role of long non-coding RNA ANRIL in the development of atherosclerosis. Noncoding RNA Res. 2022, 7, 212–216.
  52. Zhang, L.; Cheng, H.; Yue, Y.; Li, S.; Zhang, D.; He, R. H19 knockdown suppresses proliferation and induces apoptosis by regulating miR-148b/WNT/beta-catenin in ox-LDL -stimulated vascular smooth muscle cells. J. Biomed. Sci. 2018, 25, 11.
  53. Lu, G.; Chu, Y.; Tian, P. Knockdown of H19 Attenuates Ox-LDL-induced Vascular Smooth Muscle Cell Proliferation, Migration, and Invasion by Regulating miR-599/PAPPA Axis. J. Cardiovasc. Pharmacol. 2021, 77, 386–396.
  54. Safaei, S.; Tahmasebi-Birgani, M.; Bijanzadeh, M.; Seyedian, S.M. Increased Expression Level of Long Noncoding RNA H19 in Plasma of Patients with Myocardial Infarction. Int. J. Mol. Cell Med. 2020, 9, 122–129.
  55. Zhang, Z.; Gao, W.; Long, Q.Q.; Zhang, J.; Li, Y.F.; Liu, D.C.; Yan, J.J.; Yang, Z.J.; Wang, L.S. Increased plasma levels of lncRNA H19 and LIPCAR are associated with increased risk of coronary artery disease in a Chinese population. Sci. Rep. 2017, 7, 7491.
  56. Han, Y.; Ma, J.; Wang, J.; Wang, L. Silencing of H19 inhibits the adipogenesis and inflammation response in ox-LDL-treated Raw264.7 cells by up-regulating miR-130b. Mol. Immunol. 2018, 93, 107–114.
  57. Cao, L.; Zhang, Z.; Li, Y.; Zhao, P.; Chen, Y. LncRNA H19/miR-let-7 axis participates in the regulation of ox-LDL-induced endothelial cell injury via targeting periostin. Int. Immunopharmacol. 2019, 72, 496–503.
  58. Wang, X.; Che, Y.; Wang, J.; Men, K. . Xi Bao Yu Fen. Zi Mian Yi Xue Za Zhi 2023, 39, 884–890.
  59. Pan, J.X. LncRNA H19 promotes atherosclerosis by regulating MAPK and NF-kB signaling pathway. Eur. Rev. Med. Pharmacol. Sci. 2017, 21, 322–328.
  60. Qiu, S.; Sun, J. lncRNA-MALAT1 expression in patients with coronary atherosclerosis and its predictive value for in-stent restenosis. Exp. Ther. Med. 2020, 20, 129.
  61. Liu, L.; Tan, L.; Yao, J.; Yang, L. Long non-coding RNA MALAT1 regulates cholesterol accumulation in ox-LDL-induced macrophages via the microRNA-17-5p/ABCA1 axis. Mol. Med. Rep. 2020, 21, 1761–1770.
  62. Wang, L.; Qi, Y.; Wang, Y.; Tang, H.; Li, Z.; Wang, Y.; Tang, S.; Zhu, H. LncRNA MALAT1 Suppression Protects Endothelium against oxLDL-Induced Inflammation via Inhibiting Expression of MiR-181b Target Gene TOX. Oxid. Med. Cell Longev. 2019, 2019, 8245810.
  63. Huangfu, N.; Xu, Z.; Zheng, W.; Wang, Y.; Cheng, J.; Chen, X. LncRNA MALAT1 regulates oxLDL-induced CD36 expression via activating beta-catenin. Biochem. Biophys. Res. Commun. 2018, 495, 2111–2117.
  64. Shi, Z.; Zheng, Z.; Lin, X.; Ma, H. Long Noncoding RNA MALAT1 Regulates the Progression of Atherosclerosis by miR-330-5p/NF-kappaB Signal Pathway. J. Cardiovasc. Pharmacol. 2021, 78, 235–246.
  65. Ma, Z.; Zhang, J.; Xu, X.; Qu, Y.; Dong, H.; Dang, J.; Huo, Z.; Xu, G. LncRNA expression profile during autophagy and Malat1 function in macrophages. PLoS ONE 2019, 14, e0221104.
  66. Yang, J.; Lin, X.; Wang, L.; Sun, T.; Zhao, Q.; Ma, Q.; Zhou, Y. LncRNA MALAT1 Enhances ox-LDL-Induced Autophagy through the SIRT1/MAPK/NF-kappaB Pathway in Macrophages. Curr. Vasc. Pharmacol. 2020, 18, 652–662.
  67. Rusetskaya, N.Y.; Loginova, N.Y.; Pokrovskaya, E.P.; Chesovskikh, Y.S.; Titova, L.E. Redox regulation of the NLRP3-mediated inflammation and pyroptosis. Biomed. Khim 2023, 69, 333–352.
  68. Han, Y.; Qiu, H.; Pei, X.; Fan, Y.; Tian, H.; Geng, J. Low-dose Sinapic Acid Abates the Pyroptosis of Macrophages by Downregulation of lncRNA-MALAT1 in Rats With Diabetic Atherosclerosis. J. Cardiovasc. Pharmacol. 2018, 71, 104–112.
  69. Zheng, T. A Review of the Roles of Specialized Extracellular Vesicles, Migrasomes, and Exosomes in Normal Cell Physiology and Disease. Med. Sci. Monit. 2023, 29, e940118.
  70. Chen, B.; Luo, L.; Wei, X.; Gong, D.; Li, Z.; Li, S.; Tang, W.; Jin, L. M1 Bone Marrow-Derived Macrophage-Derived Extracellular Vesicles Inhibit Angiogenesis and Myocardial Regeneration Following Myocardial Infarction via the MALAT1/MicroRNA-25-3p/CDC42 Axis. Oxidative Med. Cell. Longev. 2021, 2021, 9959746.
  71. Afonso Mda, S.; Castilho, G.; Lavrador, M.S.; Passarelli, M.; Nakandakare, E.R.; Lottenberg, S.A.; Lottenberg, A.M. The impact of dietary fatty acids on macrophage cholesterol homeostasis. J. Nutr. Biochem. 2014, 25, 95–103.
  72. Gast, M.; Rauch, B.H.; Nakagawa, S.; Haghikia, A.; Jasina, A.; Haas, J.; Nath, N.; Jensen, L.; Stroux, A.; Bohm, A.; et al. Immune system-mediated atherosclerosis caused by deficiency of long non-coding RNA MALAT1 in ApoE-/-mice. Cardiovasc. Res. 2019, 115, 302–314.
  73. Huang, C.; Han, J.; Wu, Y.; Li, S.; Wang, Q.; Lin, W.; Zhu, J. Exosomal MALAT1 derived from oxidized low-density lipoprotein-treated endothelial cells promotes M2 macrophage polarization. Mol. Med. Rep. 2018, 18, 509–515.
  74. Pang, J.L.; Wang, J.W.; Hu, P.Y.; Jiang, J.S.; Yu, C. HOTAIR alleviates ox-LDL-induced inflammatory response in Raw264.7 cells via inhibiting NF-kappaB pathway. Eur. Rev. Med. Pharmacol. Sci. 2018, 22, 6991–6998.
  75. Tamanini, F.; Bontekoe, C.; Bakker, C.E.; van Unen, L.; Anar, B.; Willemsen, R.; Yoshida, M.; Galjaard, H.; Oostra, B.A.; Hoogeveen, A.T. Different targets for the fragile X-related proteins revealed by their distinct nuclear localizations. Hum. Mol. Genet. 1999, 8, 863–869.
  76. Liu, J.; Geng, X.; Hou, J.; Wu, G. New insights into M1/M2 macrophages: Key modulators in cancer progression. Cancer Cell Int. 2021, 21, 389.
  77. Italiani, P.; Boraschi, D. From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation. Front. Immunol. 2014, 5, 514.
  78. Solinas, G.; Germano, G.; Mantovani, A.; Allavena, P. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J. Leukoc. Biol. 2009, 86, 1065–1073.
  79. Erreni, M.; Mantovani, A.; Allavena, P. Tumor-associated Macrophages (TAM) and Inflammation in Colorectal Cancer. Cancer Microenviron. 2011, 4, 141–154.
  80. Karin, M.; Greten, F.R. NF-kappaB: Linking inflammation and immunity to cancer development and progression. Nat. Rev. Immunol. 2005, 5, 749–759.
  81. Wang, B.; Cheng, D.; Ma, D.; Chen, R.; Li, D.; Zhao, W.; Fang, C.; Ji, M. Mutual regulation of PD-L1 immunosuppression between tumor-associated macrophages and tumor cells: A critical role for exosomes. Cell Commun. Signal 2024, 22, 21.
  82. Seo, K.H.; Ko, H.M.; Choi, J.H.; Jung, H.H.; Chun, Y.H.; Choi, I.W.; Lee, H.K.; Im, S.Y. Essential role for platelet-activating factor-induced NF-kappaB activation in macrophage-derived angiogenesis. Eur. J. Immunol. 2004, 34, 2129–2137.
  83. Mancino, A.; Lawrence, T. Nuclear factor-kappaB and tumor-associated macrophages. Clin. Cancer Res. 2010, 16, 784–789.
  84. Varney, M.L.; Olsen, K.J.; Mosley, R.L.; Bucana, C.D.; Talmadge, J.E.; Singh, R.K. Monocyte/macrophage recruitment, activation and differentiation modulate interleukin-8 production: A paracrine role of tumor-associated macrophages in tumor angiogenesis. In Vivo 2002, 16, 471–477.
  85. Hoesel, B.; Schmid, J.A. The complexity of NF-kappaB signaling in inflammation and cancer. Mol. Cancer 2013, 12, 86.
  86. Shang, S.; Ji, X.; Zhang, L.; Chen, J.; Li, C.; Shi, R.; Xiang, W.; Kang, X.; Zhang, D.; Yang, F.; et al. Macrophage ABHD5 Suppresses NFkappaB-Dependent Matrix Metalloproteinase Expression and Cancer Metastasis. Cancer Res. 2019, 79, 5513–5526.
  87. Yu, H.; Lin, L.; Zhang, Z.; Zhang, H.; Hu, H. Targeting NF-kappaB pathway for the therapy of diseases: Mechanism and clinical study. Signal Transduct. Target. Ther. 2020, 5, 209.
  88. Chen, J.; Wu, D.; Zhang, Y.; Yang, Y.; Duan, Y.; An, Y. LncRNA DCST1-AS1 functions as a competing endogenous RNA to regulate FAIM2 expression by sponging miR-1254 in hepatocellular carcinoma. Clin. Sci. 2019, 133, 367–379.
  89. Tang, L.; Chen, Y.; Tang, X.; Wei, D.; Xu, X.; Yan, F. Long Noncoding RNA DCST1-AS1 Promotes Cell Proliferation and Metastasis in Triple-negative Breast Cancer by Forming a Positive Regulatory Loop with miR-873-5p and MYC. J. Cancer 2020, 11, 311–323.
  90. Liu, J.; Zhang, J.; Hu, Y.; Zou, H.; Zhang, X.; Hu, X. Inhibition of lncRNA DCST1-AS1 suppresses proliferation, migration and invasion of cervical cancer cells by increasing miR-874-3p expression. J. Gene Med. 2021, 23, e3281.
  91. Wang, J.; Lei, C.; Shi, P.; Teng, H.; Lu, L.; Guo, H.; Wang, X. LncRNA DCST1-AS1 Promotes Endometrial Cancer Progression by Modulating the MiR-665/HOXB5 and MiR-873-5p/CADM1 Pathways. Front. Oncol. 2021, 11, 714652.
  92. Su, Y.Z.; Cui, M.F.; Du, J.; Song, B. LncRNA DCST1-AS1 regulated cell proliferation, migration, invasion and apoptosis in gastric cancer by targeting miR-605-3p. Eur. Rev. Med. Pharmacol. Sci. 2020, 24, 1158–1167.
  93. Hu, S.; Yao, Y.; Hu, X.; Zhu, Y. LncRNA DCST1-AS1 downregulates miR-29b through methylation in glioblastoma (GBM) to promote cancer cell proliferation. Clin. Transl. Oncol. 2020, 22, 2230–2235.
  94. Huang, L.; Dai, G. Long non-coding RNA DCST1-AS1/hsa-miR-582-5p/HMGB1 axis regulates colorectal cancer progression. Bioengineered 2022, 13, 12–26.
  95. Ai, Y.; Liu, S.; Luo, H.; Wu, S.; Wei, H.; Tang, Z.; Li, X.; Zou, C. lncRNA DCST1-AS1 facilitates oral squamous cell carcinoma by promoting M2 macrophage polarization through activating NF-κB signaling. J. Immunol. Res. 2021, 2021, 5524231.
  96. He, Z.; Wang, J.; Zhu, C.; Xu, J.; Chen, P.; Jiang, X.; Chen, Y.; Jiang, J.; Sun, C. Exosome-derived FGD5-AS1 promotes tumor-associated macrophage M2 polarization-mediated pancreatic cancer cell proliferation and metastasis. Cancer Lett. 2022, 548, 215751.
  97. Lv, J.; Li, Q.; Ma, R.; Wang, Z.; Yu, Y.; Liu, H.; Miao, Y.; Jiang, S. Long Noncoding RNA FGD5-AS1 Knockdown Decrease Viability, Migration, and Invasion of Non-Small Cell Lung Cancer (NSCLC) Cells by Regulating the MicroRNA-944/MACC1 Axis. Technol. Cancer Res. Treat. 2021, 20, 1533033821990090.
  98. Zhai, W.; Ye, X.; Wang, Y.; Feng, Y.; Wang, Y.; Lin, Y.; Ding, L.; Yang, L.; Wang, X.; Kuang, Y.; et al. CREPT/RPRD1B promotes tumorigenesis through STAT3-driven gene transcription in a p300-dependent manner. Br. J. Cancer 2021, 124, 1437–1448.
  99. Xia, T.; Zhang, M.; Lei, W.; Yang, R.; Fu, S.; Fan, Z.; Yang, Y.; Zhang, T. Advances in the role of STAT3 in macrophage polarization. Front. Immunol. 2023, 14, 1160719.
  100. Liu, G.; Du, X.; Xiao, L.; Zeng, Q.; Liu, Q. Activation of fgd5-as1 promotes progression of cervical cancer through regulating bst2 to inhibit macrophage m1 polarization. J. Immunol. Res. 2021, 2021, 5857214.
  101. Neil, S.J.; Zang, T.; Bieniasz, P.D. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 2008, 451, 425–430.
  102. Kupzig, S.; Korolchuk, V.; Rollason, R.; Sugden, A.; Wilde, A.; Banting, G. Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology. Traffic 2003, 4, 694–709.
  103. Cheng, G.; Liu, D.; Liang, H.; Yang, H.; Chen, K.; Zhang, X. A cluster of long non-coding RNAs exhibit diagnostic and prognostic values in renal cell carcinoma. Aging 2019, 11, 9597–9615.
  104. Deng, Y.; Guo, K.; Tang, Z.; Feng, Y.; Cai, S.; Ye, J.; Xi, Y.; Li, J.; Liu, R.; Cai, C.; et al. Identification and experimental validation of a tumor-infiltrating lymphocytes-related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma. Front. Immunol. 2022, 13, 1046790.
  105. Shen, T.; Miao, S.; Zhou, Y.; Yi, X.; Xue, S.; Du, B.; Tang, C.; Qu, L.; Fu, D.; Jia, R.; et al. Exosomal AP000439.2 from clear cell renal cell carcinoma induces M2 macrophage polarization to promote tumor progression through activation of STAT3. Cell Commun. Signal 2022, 20, 152.
  106. Chureau, C.; Prissette, M.; Bourdet, A.; Barbe, V.; Cattolico, L.; Jones, L.; Eggen, A.; Avner, P.; Duret, L. Comparative sequence analysis of the X-inactivation center region in mouse, human, and bovine. Genome Res. 2002, 12, 894–908.
  107. Sheykhi-Sabzehpoush, M.; Ghasemian, M.; Khojasteh Pour, F.; Mighani, M.; Moghanibashi, M.; Mohammad Jafari, R.; Zabel, M.; Dziegiel, P.; Farzaneh, M.; Kempisty, B. Emerging roles of long non-coding RNA FTX in human disorders. Clin. Transl. Oncol. 2023, 25, 2812–2831.
  108. Liu, X.; Li, C.; Zhu, J.; Li, W.; Zhu, Q. Dysregulation of FTX/miR-545 signaling pathway downregulates Tim-3 and is responsible for the abnormal activation of macrophage in cirrhosis. J. Cell. Biochem. 2019, 120, 2336–2346.
  109. Liu, Z.; Dou, C.; Yao, B.; Xu, M.; Ding, L.; Wang, Y.; Jia, Y.; Li, Q.; Zhang, H.; Tu, K.; et al. Ftx non coding RNA-derived miR-545 promotes cell proliferation by targeting RIG-I in hepatocellular carcinoma. Oncotarget 2016, 7, 25350–25365.
  110. Rajagopal, T.; Talluri, S.; Akshaya, R.L.; Dunna, N.R. HOTAIR LncRNA: A novel oncogenic propellant in human cancer. Clin. Chim. Acta 2020, 503, 1–18.
  111. Xin, X.; Li, Q.; Fang, J.; Zhao, T. LncRNA HOTAIR: A Potential Prognostic Factor and Therapeutic Target in Human Cancers. Front. Oncol. 2021, 11, 679244.
  112. Wang, J.; Zhao, J.; Hu, P.; Gao, L.; Tian, S.; He, Z. Long Non-coding RNA HOTAIR in Central Nervous System Disorders: New Insights in Pathogenesis, Diagnosis, and Therapeutic Potential. Front. Mol. Neurosci. 2022, 15, 949095.
  113. Zhou, H.; Gao, L.; Yu, Z.H.; Hong, S.J.; Zhang, Z.W.; Qiu, Z.Z. LncRNA HOTAIR promotes renal interstitial fibrosis by regulating Notch1 pathway via the modulation of miR-124. Nephrology (Carlton) 2019, 24, 472–480.
  114. Yu, F.; Chen, B.; Dong, P.; Zheng, J. HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis. Mol. Ther. 2017, 25, 205–217.
  115. Price, R.L.; Bhan, A.; Mandal, S.S. HOTAIR beyond repression: In protein degradation, inflammation, DNA damage response, and cell signaling. DNA Repair (Amst) 2021, 105, 103141.
  116. Obaid, M.; Udden, S.M.N.; Alluri, P.; Mandal, S.S. LncRNA HOTAIR regulates glucose transporter Glut1 expression and glucose uptake in macrophages during inflammation. Sci. Rep. 2021, 11, 232.
  117. Ramya, V.; Shyam, K.P.; Angelmary, A.; Kadalmani, B. Lauric acid epigenetically regulates lncRNA HOTAIR by remodeling chromatin H3K4 tri-methylation and modulates glucose transport in SH-SY5Y human neuroblastoma cells: Lipid switch in macrophage activation. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2024, 1869, 159429.
  118. Zhuang, M.F.; Li, L.J.; Ma, J.B. LncRNA HOTTIP promotes proliferation and cell cycle progression of acute myeloid leukemia cells. Eur. Rev. Med. Pharmacol. Sci. 2019, 23, 2908–2915.
  119. Cheng, L.; Yang, Q.; Li, C.; Dai, L.; Yang, Y.; Wang, Q.; Ding, Y.; Zhang, J.; Liu, L.; Zhang, S.; et al. DDA1, a novel oncogene, promotes lung cancer progression through regulation of cell cycle. J. Cell Mol. Med. 2017, 21, 1532–1544.
  120. Jiang, H.; Zhou, L.; Shen, N.; Ning, X.; Wu, D.; Jiang, K.; Huang, X. M1 macrophage-derived exosomes and their key molecule lncRNA HOTTIP suppress head and neck squamous cell carcinoma progression by upregulating the TLR5/NF-kappaB pathway. Cell Death Dis. 2022, 13, 183.
  121. Cesario, A.; Rocca, B.; Rutella, S. The interplay between indoleamine 2,3-dioxygenase 1 (IDO1) and cyclooxygenase (COX)-2 in chronic inflammation and cancer. Curr. Med. Chem. 2011, 18, 2263–2271.
  122. Krawczyk, M.; Emerson, B.M. p50-associated COX-2 extragenic RNA (PACER) activates COX-2 gene expression by occluding repressive NF-kappaB complexes. eLife 2014, 3, e01776.
  123. Sun, P.; Quan, J.C.; Wang, S.; Zhuang, M.; Liu, Z.; Guan, X.; Wang, G.Y.; Wang, H.Y.; Wang, X.S. lncRNA-PACER upregulates COX-2 and PGE2 through the NF-kappaB pathway to promote the proliferation and invasion of colorectal-cancer cells. Gastroenterol. Rep. (Oxf) 2021, 9, 257–268.
  124. Desind, S.Z.; Iacona, J.R.; Yu, C.Y.; Mitrofanova, A.; Lutz, C.S. PACER lncRNA regulates COX-2 expression in lung cancer cells. Oncotarget 2022, 13, 291–306.
  125. Qian, M.; Yang, X.; Li, Z.; Jiang, C.; Song, D.; Yan, W.; Liu, T.; Wu, Z.; Kong, J.; Wei, H.; et al. P50-associated COX-2 extragenic RNA (PACER) overexpression promotes proliferation and metastasis of osteosarcoma cells by activating COX-2 gene. Tumour Biol. 2016, 37, 3879–3886.
  126. Xie, X.; Zhao, W.; Pang, J.; Xiong, X.; Wang, H.; Ma, L. Long non-coding RNA, CHRF, predicts poor prognosis of lung adenocarcinoma and promotes cell proliferation and migration. Oncol. Lett. 2018, 16, 6245–6252.
  127. Wu, Q.; Han, L.; Yan, W.; Ji, X.; Han, R.; Yang, J.; Yuan, J.; Ni, C. miR-489 inhibits silica-induced pulmonary fibrosis by targeting MyD88 and Smad3 and is negatively regulated by lncRNA CHRF. Sci. Rep. 2016, 6, 30921.
  128. Wu, W.; Wang, X.; Yu, X.; Lan, H.Y. Smad3 Signatures in Renal Inflammation and Fibrosis. Int. J. Biol. Sci. 2022, 18, 2795–2806.
  129. Luo, S.; Ding, X.; Zhao, S.; Mou, T.; Li, R.; Cao, X. Long non-coding RNA CHRF accelerates LPS-induced acute lung injury through microRNA-146a/Notch1 axis. Ann. Transl. Med. 2021, 9, 1299.
  130. Zeng, H.; Zhou, S.; Cai, W.; Kang, M.; Zhang, P. LncRNA SNHG1: Role in tumorigenesis of multiple human cancers. Cancer Cell Int. 2023, 23, 198.
  131. Li, Z.; Li, X.; Du, X.; Zhang, H.; Wu, Z.; Ren, K.; Han, X. The Interaction Between lncRNA SNHG1 and miR-140 in Regulating Growth and Tumorigenesis via the TLR4/NF-kappaB Pathway in Cholangiocarcinoma. Oncol. Res. 2019, 27, 663–672.
  132. Hu, C.; Li, J.; Tan, Y.; Liu, Y.; Bai, C.; Gao, J.; Zhao, S.; Yao, M.; Lu, X.; Qiu, L.; et al. Tanreqing Injection Attenuates Macrophage Activation and the Inflammatory Response via the lncRNA-SNHG1/HMGB1 Axis in Lipopolysaccharide-Induced Acute Lung Injury. Front. Immunol. 2022, 13, 820718.
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