Submitted Successfully!
Thank you for your contribution! You can also upload a video entry related to this topic through the link below:
Check Note
Ver. Summary Created by Modification Content Size Created at Operation
1 + 1988 word(s) 1988 2021-09-27 09:42:30 |
2 Format change Meta information modification 1988 2021-11-24 03:54:29 |
Association of miR-210 and Lung
Upload a video

MicroRNA is a class of non-coding RNA involved in post-transcriptional gene regulation. Aberrant expression of miRNAs is well-documented in molecular cancer biology. Extensive research has shown that miR-210 is implicated in the progression of multiple cancers including that of the lung, bladder, colon, and renal cell carcinoma. In recent years, exosomes have been evidenced to facilitate cell–cell communication and signaling through packaging and transporting active biomolecules such as miRNAs and thereby modify the cellular microenvironment favorable for lung cancers. MiRNAs encapsulated inside the lipid bilayer of exosomes are stabilized and transmitted to target cells to exert alterations in the epigenetic landscape. 

  • micro-RNA
  • miR-210
  • exosomes
  • lung cancer
Subjects: Allergy
Contributor :
View Times: 56
Revisions: 2 times (View History)
Update Time: 24 Nov 2021

1. Introduction

Over the past few decades, tremendous strides have been made in understanding the genetics and treatment of lung cancer. However, lung cancer remains the prevailing cause for global cancer-related morbidity and mortality [1]. Lung cancer is classified into two histological subtypes: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) [2]. NSCLC, which includes adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, is the most prevalent, covering approximately 80% of all lung cancer cases [3]. SCLC is less commonly found (15–20%) but is known to proliferate and metastasize more rapidly than NSCLC. In addition to these two main types, rare lung tumors such as carcinoid tumors, adenoid cystic carcinomas, sarcomas, and benign hamartomas have also been reported. Despite a wide array of currently available treatment methods including surgery, radiotherapy, chemotherapy, and immunotherapy, the 5-year survival rate of lung cancer patients is still under 20% [4]. Poor disease prognosis is in part due to limited understanding of the complex nature of lung tumor heterogeneity as well as late disease presentation and diagnosis. Notably, cancers are known to have long incubation periods (~20 years), during which time, the sensitivity of typical detection methods such as ultrasound, x-ray-based computer tomography, and endoscopy are inept. In recent years, liquid biopsy has become a widely used technique in clinical settings due to its ease of use, minimal invasiveness, and low cost. Most important, genomic information, such as global gene expression dysregulation, extracted from biofluids provide higher accuracy for disease detection as well as insights for underlying mechanisms of disease pathogenesis.
Aberrant expression of microRNAs (miRNAs) has been well-documented in lung cancer. Elevated oncogenic or reduced tumor suppressive miRNAs are equally important in altering cancer-related signaling pathways, and have been implicated in tumor cell growth, angiogenesis, and metastasis. In body fluids, miRNAs exist as circulating Ago protein-bound forms that are either released from damaged and dead cells or selectively packaged into extracellular vesicles (EVs) for cell signaling purposes [5][6][7]. Exosomes have been evidenced to play an important role in mediating cell–cell communication through transferring and depositing active biomolecules such as miRNAs, thereby eliciting epigenetic changes in recipient cells. Various exosomal miRNAs are dysregulated in lung cancer. In particular, miR-21, miR-31, and miR-192 are most commonly found in human lung cancer tissues and blood samples [8][9][10][11]. Through a comprehensive literature search, we find that aberrant expression of exosomal miR-210 is found across various human, cell, and animal models of lung cancer, indicating an important role in cancer development. MiR-210 is a peculiar miRNA; apart from various cancers, its dysregulation is also associated with other human diseases such as cardiovascular disease and diabetic obesity [12][13]. What is more interesting is that its inclusion in exosomes in response to hypoxia is also relevant in placental disorder preeclampsia [14].

2. Mechanisms of Exosomal miR-210 in Lung Cancer

In 2009, Rabinowits et al. first reported that miRNAs extracted from NSCLC tissue can serve as diagnostic biomarkers [15][16]. Since then, various miRNAs have been implicated in the development of lung cancer, and miR-21 has been one of the most extensively studied candidates. However, while dysregulation of exosomal miR-210 has been reported in human, cell, and animal studies (Table 1), less is known about its underlying mechanisms in lung cancer. This section will examine all currently known mechanistic pathways involved in exosomal miR-210-mediated lung cancer.
Table 1. MiR-210 expression in human, cell, and mouse models.
Exosomal miRNA miR-210 miR-210-3p miR-210-3p miR-210-3p miR-210 miR-210
Expression Level Up Up Up Up Up Up
Sample Source Human Cell Cell Cell Cell Fox Chase SCID mice
Sample Type Pleural effusion HCC827 cells, PC-9 cells, HCC827-OR cells, PC-9-OR cells H358 cells, A549 cells, H460 cells A549 cells, NCIH1703 cells, BEAS-2B cells A549 cells, HEK-293/EBNA cells Plasma
Exosome Isolation Method Exosome isolation reagents (Invitrogen) differential centrifugation EXO Quick ultracentrifugation ExoQuick-TC ExoQuick-TC
miRNA Detection Method qRT-PCR miRNA microarray and qRT-PCR miRNA microarray qRT-PCR qRT-PCR qRT-PCR
Upstream Regulator unknown unknown unknown unknown TIMP-1 TIMP-1
Downstream Target unknown unknown STAT3 signalling FGFRL1 EphA3 FGFRL1, E2F3, VMP-1, RAD52 and SDHD
Function unknown Drug resistance Invasion, Metastasis, EMT pro-proliferative Angiogenesis Vascularization
Cancer Type adenocarcinoma NSCLC NSCLC Not specified adenocarcinoma adenocarcinoma
Reference [9] [17] [18] [19] [20] [21]

2.1. Signal Transducer and Activator of Transcription 3 (STAT3)

Hypoxic bone marrow-derived mesenchymal stem cells (BMSCs) have been evidenced to transfer exosomal miRNAs to promote lung cancer metastasis. Specifically, lung cancer cells (A549, LLC, H460, and H358) treated with hypoxic BMSC-derived exosomes demonstrated increased migration and invasion potentials compared to normoxic BMSC-secreted exosomes [18]. Hypoxic BMSC-derived exosomes were especially rich in miR-193a-3p, miR-210-3p, and miR-5100. Furthermore, BMSC-derived exosomes promoted both the total and phosphorylated STAT3 levels [18]. STAT3 is known to be overexpressed in cancer cells, and functions to elicit production of immunosuppressive factors. Moreover, miR-210-3p inhibitor was capable of reducing phosphorylated STAT3 expression. The study further analyzed plasma exosomes and found significantly upregulated miR-210-3p levels in metastatic lung cancer patients compared to non-metastatic lung cancer patients and healthy controls, suggesting that miR-210 may play an important role in lung metastasis. Specifically, miR-210-3p is capable of targeting STAT3 inhibitor, suppressor of cytokine signaling 1 (SOCS1) [22]. Interestingly, miR-210-5p has also been shown to directly target SOCS1 in RCC [23].

2.2. Fibroblast Growth Factor Receptor Like 1 (FGFRL1)

Cancer cells have high heterogeneity and contain a variety of cell types. Cancer stem cells (CSCs) for example, make up a small population of cancer cells, and are characterized by enhanced self-renewal and chemo/radiotherapy resistance capabilities, which make them the main mediators for sustained cancer growth. Lung CSC-derived exosomes have been evidenced to contain high levels of miR-210-3p and enhance lung cancer cell migration and invasion, through the inhibition of E-cadherin as well as the promotion of vimentin, N-cadherin, MMP-9, and MMP-1 expression, which are phenotypic hallmarks for EMT and enhanced invasive potential [19]. Moreover, the study indicated that miR-210-3p may contribute to cancer cell metastasis via the inhibition of FGFRL1. FGFRL1 is part of the FGFR family and has been reported to modulate ERK1/2 and FGF signaling pathways [24]. Recently, FGFRL1 has been associated with prostate, gastric, oesophageal, and ovarian cancer cell proliferation and metastasis [25][26]. In particular, miR-210 has been evidenced to promote angiogenesis by targeting FGFRL1 in hepatocellular carcinoma and osteosarcoma cells [27][28]. However, in oesophageal squamous cell carcinoma, laryngocarcinoma, and bladder cancer, miR-210-3p has showed tumor suppressive properties through FGFRL1 binding [29][27][30]. These conflicting results suggest that miR-210-3p and FGFRL1 may have dual roles in cancer.

2.3. PI3K/AKT Pathway

Runt-related transcription factor-3 (RUNX3) is primarily involved in cartilage mineralization and chondrocyte maturation, though evidence suggests that miRNA-regulated RUNX3 is capable of influencing phosphatidylinositol-3-kinase protein kinase B (PI3K/AKT) signaling pathway, which is crucial for cancer cell proliferation [31][32][33]. RUNX3 is correlated with poor prognosis and shorter survival in NSCLC patients [34][35]. A study led by Li et al. reported that miR-210 was capable of inhibiting RUNX3, thereby activating PI3K/AKT signaling pathway and promoting malignant phenotype of lung cancer cells [35]. Conversely, the inhibition of miR-210 or PI3K/AKT signaling pathway via LY294002 treatment reversed malignant potential of lung cancer cells. In addition to RUNX3, PTEN is another well-known regulator of the PI3K/AKT signaling pathway. For example, overexpression of miR-210 has been shown to promote NSCLC cell migration and invasion through UPF1 suppression followed by upregulation of the PTEN/PI3K/AKT pathway [36]. More recently, miR-210 upregulation has been reported to inhibit upstream stimulating factor 1 (USF-1) and polycomb group ring (PCGF3) [37]. USF-1 is a transcription factor belonging to the basic helix-loop-helix leucine zipper family, and is known to regulate hepatocellular carcinoma, papillary thyroid as well as lung cancer [38]. Interestingly, PCGF3 has also been reported to promote cell proliferation in NSCLC via the PI3K/AKT signaling pathway [39]. Moreover, miR-210-mediated PI3K/AKT signaling has also been reported in oral cancer. Notably, in oral squamous cell carcinoma, elevated exosomal miR-210-3p levels can inhibit ephrinA3 expression and in turn activate PI3K/AKT signaling pathway [40]. Overall, these studies suggest that miR-210 can alter PI3K/AKT through various factors, and that this phenomenon is not limited to lung cancer.

2.4. Tissue Inhibitor of Metalloproteinases-1 (TIMP-1)

TIMP-1 is known to regulate protease homeostasis via the inhibition of metzincin [41][42]. Its ability to inhibit matrix metalloproteinases (MMPs) and A-disintegrin-and-metalloproteinase (ADAM-10) reflect anti-tumorigenic characteristics. However, increased TIMP-1 expression is often correlated with poor prognosis, especially in ovarian, lung, gastric, and papillary thyroid carcinoma [43][44][45][46][47][48]. Interestingly, TIMP-1 serves as a positive regulator of PI3Ks and has been evidenced to promote cancer cell growth via AKT/ERK phosphorylation [49][50][51][52][53]. A study led by Cui et al. showed that an increase in TIMP-1 promoted lung cancer progression through activating the PI3K/AKT/HIF-1 signaling pathway and miR-210 expression [21]. Specifically, high levels of miR-210 were found in exosomes derived from TIMP-1 overexpressing A549L cells, and that its expression level was dependent on HIF-1 accumulation. Conversely, a reduction in miR-210 can effectively inhibit A549L cell growth, suggesting its important role in cancer cell proliferation. Previous research has reported that hypoxia promotes exosome secretion of miR-210, suggesting a mechanism of a self-sustaining hypoxia state. Moreover, the study finds that levels of mature miR-210 was dependent on CD63, an interacting partner of TIMP-1, providing novel insight into the mechanism of elevated miR-210 in lung cancer.

2.5. Epidermal Growth Factor Receptor (EGFR)-Mutant Drug Resistance

Osimertinib is a tyrosine kinase inhibitor, specifically designed to treat EGFR-mutant non-small cell lung cancer [54][55]. Despite its effectiveness compared to previous two generations of EGFR-tyrosine kinase inhibitors (EGFR-TKIs), multiple studies have reported resistance to osimertinib, due to varying mechanisms, including EGFR mutation, KRAS mutation, BRAF mutation, loss of T900M mutation, or HER2 amplification [56]. Using microarray and qRT-PCR, Hisakane et al. reported high levels of exosomal miR-210 in osimertinib-resistant HCC827-OR and PC-9-OR cells compared to HCC827 and PC-9 parental cells [17]. Moreover, co-culturing exosomes isolated from osimertinib-resistant cells as well as induction of miR-210 both led to drug resistance and EMT in oximertinib-sensitive cells. However, there was no evidence that miR-210 acted via the EGFR signaling pathway, suggesting the involvement of a bypass mechanism. The study points to E-cadherin as a potential mediating factor associated with EMT. In addition, exosomes isolated from colorectal cancer cells and pancreatic cancer stem cells have also been found to carry high abundance of miR-210 and are correlated with fluorouacil and gemcitabine resistance [57][58][59].


Mutant KRAS is a well-known driver of lung neoplasia, part of which functions through secreting exosomes to manipulate tumor microenvironment favorable for hypoxic immunosuppression [60][61][62]. Interestingly, in KRAS chemoresistant lung cancer tissues from human patients, high abundance of miR-146 and miR-210 were found compared to non-KRAS metastatic samples [62]. Moreover, post KRAS exosome inhibition, miR-210 expression levels were reduced, suggesting a direct relationship between KRAS and miR-210 levels. In addition, levels of miR-146/miR-210 were found at lower levels in lymph node metastatic tissues, indicating their importance in primary lung tumor. The study went on to report that KRAS was capable of regulating chromatin remodeling genes SMARCE1/NCOR1, which play key roles in chemosresistant metastasis, as well as transcription factor BACH2/GATA-3 expression through pyruvate/PKM2-dependent metabolism, thereby contributing to sustained immunosuppressive metastasis [62]. Although the mechanism of how miR-210 is regulated by KRAS remains elusive, there is clear evidence that PKM2 is an HIF-1 target gene [63].


  1. Fan, T.; Sun, N.; He, J. Exosome-Derived LncRNAs in Lung Cancer. Front. Oncol. 2020, 10, 1728.
  2. Alipoor, S.D.; Mortaz, E.; Varahram, M.; Movassaghi, M.; Kraneveld, A.D.; Garssen, J.; Adcock, I.M. The Potential Biomarkers and Immunological Effects of Tumor-Derived Exosomes in Lung Cancer. Front. Immunol. 2018, 9, 819.
  3. Masaoutis, C.; Mihailidou, C.; Tsourouflis, G.; Theocharis, S. Exosomes in lung cancer diagnosis and treatment. From the translating research into future clinical practice. Biochimie 2018, 151, 27–36.
  4. Iqbal, M.A.; Arora, S.; Prakasam, G.; Calin, G.A.; Syed, M.A. MicroRNA in lung cancer: Role, mechanisms, pathways and therapeutic relevance. Mol. Aspects Med. 2019, 70, 3–20.
  5. de Miguel Pérez, D.; Martínez, A.R.; Palomo, A.O.; Ureña, M.D.; Puche, J.L.G.; Remacho, A.R.; Hernandez, J.E.; Acosta, J.A.L.; Sánchez, F.G.O.; Serrano, M.J. Extracellular vesicle-miRNAs as liquid biopsy biomarkers for disease identification and prognosis in metastatic colorectal cancer patients. Sci. Rep. 2020, 10, 1–13.
  6. Ferracin, M.; Lupini, L.; Salamon, I.; Saccenti, E.; Zanzi, M.V.; Rocchi, A.; Da, R.L.; Zagatti, B.; Musa, G.; Bassi, C.; et al. Absolute quantification of cell-free microRNAs in cancer patients. Oncotarget 2015, 6, 14545–14555.
  7. Turchinovich, A.; Tonevitsky, A.G.; Burwinkel, B. Extracellular miRNA: A Collision of Two Paradigms. Trends Biochem. Sci. 2016, 41, 883–892.
  8. Guan, P.; Yin, Z.; Li, X.; Wu, W.; Zhou, B. Meta-analysis of human lung cancer microRNA expression profiling studies comparing cancer tissues with normal tissues. J. Exp. Clin. Cancer Res. 2012, 31, 54.
  9. Tamiya, H.; Mitani, A.; Saito, A.; Ishimori, T.; Saito, M.; Isago, H.; Jo, T.; Yamauchi, Y.; Tanaka, G.; Nagase, T. Exosomal MicroRNA Expression Profiling in Patients with Lung Adenocarcinoma-associated Malignant Pleural Effusion. Anticancer Res. 2018, 38, 6707–6714.
  10. Ulivi, P.; Zoli, W. miRNAs as Non-Invasive Biomarkers for Lung Cancer Diagnosis. Molecules 2014, 19, 8220–8237.
  11. Võsa, U.; Vooder, T.; Kolde, R.; Vilo, J.; Metspalu, A.; Annilo, T. Meta-analysis of microRNA expression in lung cancer. Int. J. Cancer 2013, 132, 2884–2893.
  12. Tian, F.; Tang, P.; Sun, Z.L.; Zhang, R.F.; Zhu, D.H.; He, J.Y.; Liao, J.X.; Wan, Q.H.; Shen, J. miR-210 in exosomes derived from macrophages under high glucose promotes mouse diabetic obesity pathogenesis by suppressing NDUFA4 expression. J. Diabetes Res. 2020, 2020, 689486.
  13. Wang, L.R.; Jia, Q.J.; Chen, X.N.; Xie, Y.Y.; Yang, Y.Q.; Zhang, A.; Liu, R.T.; Zhuo, Y.; Zhang, J.P. Role of cardiac progenitor cell-derived exosome-mediated microRNA-210 in cardiovascular disease. J. Cell. Mol. Med. 2019, 23, 7124–7131.
  14. Biró, O.; Fóthi, Á.; Alasztics, B.; Nagy, B.; Orbán, T.I.; Rigó, J. Circulating exosomal and Argonaute-bound microRNAs in preeclampsia. Gene 2019, 692, 138–144.
  15. Hu, C.; Meiners, S.; Lukas, C.; Stathopoulos, G.T.; Chen, J. Role of exosomal microRNAs in lung cancer biology and clinical applications. Cell Prolif. 2020, 53, e12828.
  16. Rabinowits, G.; Gerel-Taylor, C.; Day, J.M.; Taylor, D.D.; Kloecker, G.H. Exosomal MicroRNA: A Diagnostic Marker for Lung Cancer. Clin. Lung Cancer 2009, 10, 42–46.
  17. Hisakane, K.; Seike, M.; Sugano, T.; Yoshikawa, A.; Matsuda, K.; Takano, N.; Takahashi, S.; Noro, R.; Gemma, A. Exosome-derived miR-210 involved in resistance to osimertinib and epithelial–mesenchymal transition in EGFR mutant non-small cell lung cancer cells. Thorac. Cancer 2021, 12, 1690–1698.
  18. Zhang, X.; Sai, B.; Wang, F.; Wang, L.; Wang, Y.; Zheng, L.; Li, G.; Tang, J.; Xiang, J. Hypoxic BMSC-derived exosomal miRNAs promote metastasis of lung cancer cells via STAT3-induced EMT. Mol. Cancer 2019, 18, 40.
  19. Wang, L.; He, J.; Hu, H.; Tu, L.; Sun, Z.; Liu, Y.; Luo, F. Lung CSC-derived exosomal miR-210-3p contributes to a pro-metastatic phenotype in lung cancer by targeting FGFRL1. J. Cell. Mol. Med. 2020, 24, 6324–6339.
  20. Cui, H.; Sebastien, G.; Florian, S.; Bernard, M.; Achim, K. On the Pro-Metastatic Stress Response to Cancer Therapies: Evidence for a Positive Co-Operation between TIMP-1, HIF-1α, and miR-210. Front. Pharmacol. 2012, 3, 134.
  21. Cui, H.; Seubert, B.; Stahl, E.; Dietz, H.; Reuning, U.; Moreno-Leon, L.; Ilie, M.; Hofman, P.; Nagase, H.; Mari, B.; et al. Tissue inhibitor of metalloproteinases-1 induces a pro-tumourigenic increase of miR-210 in lung adenocarcinoma cells and their exosomes. Oncogene 2015, 34, 3640–3650.
  22. Ren, D.; Yang, Q.; Dai, Y.; Guo, W.; Du, H.; Song, L.; Peng, X. Oncogenic miR-210-3p promotes prostate cancer cell EMT and bone metastasis via NF-kB signaling pathway. Mol. Cancer 2017, 16, 117.
  23. Xiao, H.; Shi, J. Exosomal circular RNA_400068 promotes the development of renal cell carcinoma via the miR-210-5p/SOCS1 axis. Mol. Med. Rep. 2020, 6, 4810–4820.
  24. Chen, R.; Li, D.; Zheng, M.; Chen, B.; Wei, T.; Wang, Y.; Li, M.; Huang, W.; Tong, Q.; Wang, Q. FGFRL1 affects chemoresistance of small-cell lung cancer by modulating the PI3K/Akt pathway via ENO1. J. Cell. Mol. Med. 2020, 24, 2123–2134.
  25. Liu, Q.; Hu, S.; Li, X.; Yan, S.; Tan, H. MiRNA-495 inhibits cell proliferation and invasion abilities in gastric cancer cells by down-regulation of FGFRL1. Int. J. Clin. Exp. Pathol. 2016, 9, 7867–7877.
  26. Tai, H.; Wu, Z.; Sun, S.; Zhang, Z.; Xu, C. FGFRL1 Promotes Ovarian Cancer Progression by Crosstalk with Hedgehog Signaling. J. Immunol. Res. 2018, 2018, 1–11.
  27. Costales, M.G.; Haga, C.L.; Velagapudi, S.P.; Childs-Disney, J.L.; Phinney, D.G.; Disney, M.D. Small Molecule Inhibition of microRNA-210 Reprograms an Oncogenic Hypoxic Circuit. J. Am. Chem. Soc. 2017, 139, 3446–3455.
  28. Kelly, T.J.; Souza, A.L.; Clish, C.B.; Puigserver, P. A hypoxia-induced positive feedback loop promotes hypoxia-inducible factor 1alpha stability through miR-210 suppression of glycerol-3-phosphate dehydrogenase 1-like. Mol. Cell. Biol. 2011, 31, 2696–2706.
  29. Ying, Q.; Liang, L.; Guo, W.; Zha, R.; Tian, Q.; Huang, S.; Yao, J.; Ding, J.; Bao, M.; Ge, C. Hypoxia-inducible MicroRNA-210 augments the metastatic potential of tumor cells by targeting vacuole membrane protein 1 in hepatocellular carcinoma. Hepatology 2011, 54, 2064–2075.
  30. Cheng, H.H.; Mitchell, P.S.; Kroh, E.M.; Dowell, A.E.; Tewari, M. Circulating microRNA Profiling Identifies a Subset of Metastatic Prostate Cancer Patients with Evidence of Cancer-Associated Hypoxia. PLoS ONE 2013, 8, e69239.
  31. Wei, J.; Gou, Z.; Wen, Y.; Luo, Q.; Huang, Z. Marine compounds targeting the PI3K/Akt signaling pathway in cancer therapy. Biomed. Pharmacother. 2020, 129, 110484.
  32. Zhou, Z.; Yao, B.; Zhao, D. Runx3 regulates chondrocyte phenotype by controlling multiple genes involved in chondrocyte proliferation and differentiation. Mol. Biol. Rep. 2020, 47, 5773–5792.
  33. Chen, X.; Deng, Y.; Yi, S.; Zhu, W.; Weng, G. Loss of expression rather than cytoplasmic mislocalization of RUNX3 predicts worse outcome in non-small cell lung cancer. Oncol. Lett. 2018, 15, 5043–5055.
  34. Li, Z.B.; Chen, X.; Yi, X.J. Tumor promoting effects of exosomal microRNA-210 derived from lung cancer cells on lung cancer through the RUNX3/PI3K/AKT signaling pathway axis. J. Biol. Reg. Homeost. Agents 2021, 35, 473–484.
  35. Yang, F.; Yan, Y.B.; Yang, Y.; Xuan, H.; Wang, M.; Yang, Z.Y.; Liu, B.G.; Ye, L.G. MiR-210 in exosomes derived from CAFs promotes non-small cell lung cancer migration and invasion through PTEN/PI3K/AKT pathway. Cell. Sig. 2020, 73, 109675.
  36. Chen, Q.; Zhang, H.Y.; Zhang, J.Y.; Shen, L.; Yang, J.; Wang, Y.; Ma, J.X.; Zhuan, B. miR-210-3p Promotes Lung Cancer Development and Progression by Modulating USF1 and PCGF3. OncoTargets Ther. 2021, 14, 3687.
  37. Kim, K.C.; Yun, J.; Son, D.J.; Kim, J.Y.; Jung, J.K.; Choi, J.S.; Kim, Y.R.; Song, J.K.; Kim, S.Y.; Kang, S.K.; et al. Suppression of metastasis through inhibition of chitinase 3-like 1 expression by miR-125a-3p-mediated up-regulation of USF1. Theranostics 2018, 16, 4409.
  38. Hu, Y.; Cheng, Y.; Jiang, X.; Zhang, Y.; Wang, H.; Ren, H.; Xu, Y.; Jiang, J.; Wang, Q.; Su, H.; et al. PCGF3 promotes the proliferation and migration of non-small cell lung cancer cells via the PI3K/AKT signaling pathway. Exp. Cell Res. 2021, 400, 112496.
  39. Wang, H.; Wang, L.; Zhou, X.C.; Luo, X.Y.; Liu, K.; Jiang, E.H.; Chen, Y.; Shao, Z.; Shang, Z.J. OSCC exosomes regulate miR-210-3p targeting EFNA3 to promote oral cancer angiogenesis through the PI3K/AKT pathway. BioMed Res. Int. 2020, 2125656.
  40. Brew, K.; Nagase, H. The tissue inhibitors of metalloproteinases (TIMPs): An ancient family with structural and functional diversity. Biochim. Biophys. Acta BBA Mol. Cell Res. 2010, 1803, 55–71.
  41. Murphy, G. Tissue inhibitors of metalloproteinases. Genome Biol. 2011, 12, 233.
  42. Ilie, M.; Lassalle, S.; Long-Mira, E. In papillary thyroid carcinoma, TIMP-1 expression correlates with BRAF (V600E) mutation status and together with hypoxia-related proteins predicts aggressive behavior. Virchows Arch. 2013, 463, 437–444.
  43. Pesta, M.; Kulda, V.; Kucera, R.; Pesek, M.; Topolcan, O. Prognostic Significance of TIMP-1 in Non-small Cell Lung Cancer. Anticancer Res. 2011, 31, 4031–4038.
  44. Rauvala, M.; Puistola, U.; Turpeenniemi-Hujanen, T. Gelatinases and their tissue inhibitors in ovarian tumors; TIMP-1 is a predictive as well as a prognostic factor. Gynecol. Oncol. 2005, 99, 656–663.
  45. Wang, C.S.; Wu, T.L.; Tsao, K.C.; Sun, C.F. Serum TIMP-1 in gastric cancer patients: A potential prognostic biomarker. Ann. Clin. Lab. Sci. 2006, 36, 23–30.
  46. Ylisirni, S.; Hyhty, M.; MKitaro, R.; Pakk, P.; Risteli, J.; Kinnula, V.L.; Turpeenniemi-Hujanen, T.; Jukkola, A. Elevated serum levels of type I collagen degradation marker ICTP and tissue inhibitor of metalloproteinase (TIMP) 1 are associated with poor prognosis in lung cancer. Clin. Cancer Res. 2001, 7, 1633–1637.
  47. Ylisirniö, S.; Höyhtyä, M.; Turpeenniemi-Hujanen, T. Serum matrix metalloproteinases -2, -9 and tissue inhibitors of metalloproteinases -1, -2 in lung cancer--TIMP-1 as a prognostic marker. Anticancer Res. 2000, 20, 1311–1316.
  48. Jung, K.K.; Liu, X.W.; Chirco, R.; Fridman, R.; Kim, H. Identification of CD63 as a tissue inhibitor of metallonproteinase-1 interacting cell surface protein. EMBO J. 2006, 25, 3934–3942.
  49. Li, G.Y.; Fridman, R.; Kim, H. Tissue Inhibitor of Metalloproteinase-1 Inhibits Apoptosis of Human Breast Epithelial Cells. Cancer Res. 1999, 59, 6267–6275.
  50. Liu, X.W.; Bernardo, M.M.; Fridman, R.; Kim, H. Tissue Inhibitor of Metalloproteinase-1 Protects Human Breast Epithelial Cells Against Intrinsic Apoptotic Cell Death via the Focal Adhesion Kinase/Phosphatidylinositol 3-Kinase and MAPK Signaling Pathway. J. Biol. Chem. 2003, 278, 40364–40372.
  51. Liu, X.W.; Taube, M.E.; Jung, K.K.; Dong, Z.; Kim, H. Tissue Inhibitor of Metalloproteinase-1 Protects Human Breast Epithelial Cells from Extrinsic Cell Death: A Potential Oncogenic Activity of Tissue Inhibitor of Metalloproteinase-1. Cancer Res. 2005, 65, 898–906.
  52. Taube, M.E.; Liu, X.W.; Fridman, R.; Kim, H. TIMP-1 regulation of cell cycle in human breast epithelial cells via stabilization of p27KIP1 protein. Oncogene 2006, 25, 3041.
  53. Mok, T.S.; Wu, Y.L.; Ahn, M.J.; Garassino, M.C.; Kim, H.R.; Ramalingam, S.S.; Shepherd, F.A.; He, Y.; Akamatsu, H.; Theelen, W. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N. Engl. J. Med. 2017, 376, 629–640.
  54. Soria, J.C.; Ohe, Y.; Vansteenkiste, J.; Reungwetwattana, T.; Chewaskulyong, B.; Lee, K.H.; Dechaphunkul, A.; Imamura, F.; Nogami, N.; Kuratal, T. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2018, 378, 113.
  55. Leonetti, A.; Sharma, S.; Minari, R.; Perego, P.; Tiseo, M. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br. J. Cancer 2019, 121, 1–13.
  56. Anke, N.; Hannah, T.; Julie, A.; Alexandra, P.; Luke, G.; Amy, L.; Bundy, J.G.; Tomoyoshi, S.; Aisha, J.; David, P. Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance. Hum. Mol. Genet. 2017, 26, 1552.
  57. Runglawan, S.; Yingpinyapat, K.; Suyanee, T.; Watcharin, L.; Anchalee, T.; Piti, U.; Narong, K.; Puangrat, Y.; Yang, J.H.; Hee, K.N. Potential role of HIF-1-responsive microRNA210/HIF3 axis on gemcitabine resistance in cholangiocarcinoma cells. PLoS ONE 2018, 13, e199827.
  58. Yang, Z.; Zhao, N.; Cui, J.; Wu, H.; Xiong, J.; Peng, T. Exosomes derived from cancer stem cells of gemcitabine-resistant pancreatic cancer cells enhance drug resistance by delivering miR-210. Cell. Oncol. 2020, 43, 123–136.
  59. Kerr, E.M.; Martins, C.P. Metabolic rewiring in mutant Kras lung cancer. FEBS J. 2018, 285, 28–41.
  60. Shen, H.; Che, K.; Lei, C.; Wei, D.; Du, J. Diagnostic and prognostic value of blood samples for KRAS mutation identification in lung cancer: A meta-analysis. Oncotarget 2017, 8, 36812–36823.
  61. Vasan, N.; Boyer, J.L.; Herbst, R.S. A RAS Renaissance: Emerging Targeted Therapies for KRAS-Mutated Non-Small Cell Lung Cancer. Clin. Caner Res. 2014, 20, 3921–3930.
  62. Petanidis, S.; Domvri, K.; Porpodis, K.; Anestakis, D.; Zarogoulidis, K. Inhibition of kras-derived exosomes downregulates immunosuppressive BACH2/GATA-3 expression via RIP-3 dependent necroptosis and miR-146/miR-210 modulation ART ICLE IN FO. Biomed. Pharmacother. 2020, 122, 109461.
  63. Luo, W.B.; Hu, H.X.; Ryan, C.; Zhong, J.; Matthew, K.; Robert, O.M.; Robert, N.C.; Pandey, A.; Semenza, G.L. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 2011, 145, 732–744.
Subjects: Allergy
Contributor :
View Times: 56
Revisions: 2 times (View History)
Update Time: 24 Nov 2021
Table of Contents


    Are you sure to Delete?

    Video Upload Options

    Do you have a full video?
    If you have any further questions, please contact Encyclopedia Editorial Office.
    Chen, Q.Y. Association of miR-210 and Lung. Encyclopedia. Available online: (accessed on 05 July 2022).
    Chen QY. Association of miR-210 and Lung. Encyclopedia. Available at: Accessed July 05, 2022.
    Chen, Qiao Yi. "Association of miR-210 and Lung," Encyclopedia, (accessed July 05, 2022).
    Chen, Q.Y. (2021, November 24). Association of miR-210 and Lung. In Encyclopedia.
    Chen, Qiao Yi. ''Association of miR-210 and Lung.'' Encyclopedia. Web. 24 November, 2021.