Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Bojana Kožik
 -- 2683 2023-11-23 14:25:17 |
2 Reference format revised.
Lindsay Dong
 + 2 word(s) 2685 2023-11-24 07:36:42 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Krajnović, M.; Kožik, B.; Božović, A.; Jovanović-Ćupić, S. RUNX Gene Family in Hepatocellular Carcinoma. Encyclopedia. Available online: https://encyclopedia.pub/entry/51998 (accessed on 02 September 2024).
Krajnović M, Kožik B, Božović A, Jovanović-Ćupić S. RUNX Gene Family in Hepatocellular Carcinoma. Encyclopedia. Available at: https://encyclopedia.pub/entry/51998. Accessed September 02, 2024.
Krajnović, Milena, Bojana Kožik, Ana Božović, Snežana Jovanović-Ćupić. "RUNX Gene Family in Hepatocellular Carcinoma" Encyclopedia, https://encyclopedia.pub/entry/51998 (accessed September 02, 2024).
Krajnović, M., Kožik, B., Božović, A., & Jovanović-Ćupić, S. (2023, November 23). RUNX Gene Family in Hepatocellular Carcinoma. In Encyclopedia. https://encyclopedia.pub/entry/51998
Krajnović, Milena, et al. "RUNX Gene Family in Hepatocellular Carcinoma." Encyclopedia. Web. 23 November, 2023.
RUNX Gene Family in Hepatocellular Carcinoma
Edit
This entry is adapted from the peer-reviewed paper 10.3390/cells12182303

Hepatocellular carcinoma (HCC) is one of the most frequent cancers in humans, characterised by a high resistance to conventional chemotherapy, late diagnosis, and a high mortality rate. It is necessary to elucidate the molecular mechanisms involved in hepatocarcinogenesis to improve diagnosis and treatment outcomes. The Runt-related (RUNX) family of transcription factors (RUNX1, RUNX2, and RUNX3) participates in cardinal biological processes and plays paramount roles in the pathogenesis of numerous human malignancies. Their role is often controversial as they can act as oncogenes or tumour suppressors and depends on cellular context. Evidence shows that deregulated RUNX genes may be involved in hepatocarcinogenesis from the earliest to the latest stages.

RUNX hepatocellular carcinoma oncogenes tumour suppressors biomarkers

1. Introduction

Hepatocellular carcinoma is a primary liver cancer and one of the leading causes of mortality with wide geographic variation [1]. Any factor that leads to chronic liver injury and cirrhosis can be considered an oncogenic agent. Prevalent hepatocellular carcinoma (HCC) risk factors are Hepatitis viruses B and C infection, excessive alcohol intake, nonalcoholic steatohepatitis (NASH), and aflatoxin B1 exposure [2][3].
The major problem with the HCC treatment is the diagnosis is usually made in progressed disease stadiums when conventional systemic chemotherapy is ineffective [4]. To overcome this problem, researchers are developing molecularly targeted treatments that represent a more promising approach for advanced HCC. Several such drugs are clinically available, but their efficacy is limited [5]. Therefore, elucidating the molecular processes at the basis of hepatocarcinogenesis is critical for improving therapy outcomes and diagnosis.
The family of Runt-related (RUNX) genes (RUNX1, RUNX2, and RUNX3) is crucial for the different tumour types’ development and progression. RUNX proteins are transcription factors that behave in opposing ways, promoting or suppressing tumourigenesis [6][7][8]. However, the exact mechanisms of their deregulation in HCC, especially for RUNX1 and RUNX2, have not yet been sufficiently investigated.

1.1. RUNX Genes’ and Proteins’ Structure

Human RUNX genes participate in neuro-, blood, and bone development [7][8]. The role in developmental processes implies tight control of RUNX genes at transcriptional and posttranscriptional levels. RUNX genes’ chromosome location differs depending on the species, and human RUNX1, RUNX2, and RUNX3 genes’ locations are on chromosomes 21, 6, and 1, respectively. Two alternative promoters of RUNX genes, P1 and P2, generate two dominant isoforms with differing 5′-untranslated regions (5′-UTRs) (Figure 1A). These transcripts give two polypeptides with different N-terminal sequences, distal and proximal [9]. The diversity of RUNX transcripts is the result of alternative splicing. RUNX1 and RUNX2 have nine exons and twelve isoforms, whereas RUNX3 has six exons and two isoforms [7][10]. RUNX proteins’ molecular weight is 44, 50, and 57 KDa [7].
Cells 12 02303 g001
Figure 1. The structures of RUNX1, RUNX2, and RUNX3 genes and proteins. (A) RUNX1, RUNX2, and RUNX3 genes’ structure. Rectangles—exons; lines—introns; ATG—start codon; P1 and P2—promoters, RHD—Runt homology domain; and TAD—transactivation domain. Grey rectangles—untranslated regions. (B) RUNX1, RUNX2, and RUNX3 proteins’ structure. Rectangles—protein domains. Numbers—amino acids’ numbers. NLS—nuclear localisation signal; QA—the glutamine/alanine-rich signal, RUNX2 specific; ID—inhibitory domain; and VWRPY—Groucho/TLE binding site. The figure is a not-to-scale drawing. The figure is created under CC BY NC, based on Yi et al., 2022 [10].
RUNX proteins received their name from the Runt homology domain (RHD) on the protein N-terminus, which has approximately 90% sequence homology in all three proteins [6]. The RHD domain binds to the target genes’ DNA through the consensus sequence of seven nucleotides, ‘PyGPyGGTPy’. Nuclear localisation and interaction with the other proteins are also functions of the RHD domain [10]. The RUNX proteins’ C-terminus encompasses the transactivation domain (TAD) and inhibitory domain (ID), with the consensus sequence of five amino acids, valine–tryptophan–arginine–proline–tyrosine (VWRPY). This sequence recruits Groucho/Transducin-like enhancer protein (TLE) corepressors [7][10][11]. TLE corepressors further control several target genes’ transcription. The TAD domain is the place of RUNX proteins’ interactions with the other regulatory proteins and control of their transcriptional activity [12]. In complex with the coregulators, RUNX proteins influence various cell processes [10] (Figure 1B).

1.2. The Role of the RUNX Genes in Normal Development

RUNX genes engage in normal cell development and differentiation processes, playing a tissue-specific role [13]. RUNX1 is crucial for cell growth and differentiation of immune cells, epithelial stem and epithelial cells, and neurodevelopment [11][14]. RUNX1 acts in the development of hematopoietic cells in vertebrates [15][16]. Consequently, the chromosomal rearrangements and gene mutations involving RUNX1 lead to various leukaemia types [15]. RUNX2 is a factor in bone generation [11]. RUNX2 knockout mice lack osteoblast differentiation, leading to osteoporosis [17]. RUNX3 is essential for embryogenesis, and RUNX3 knockout mice die quickly [18].

1.3. The Role of RUNX Genes in Cancer

RUNX genes’ mutations and abnormal expression lead to various cancer types. RUNX genes can hinder or activate tumourigenesis [12]. A recent study by Pan and colleagues [19] suggests that RUNX genes’ aberrant expression causes disparate cancer types and influences disease prognosis.
RUNX1 plays a cardinal role in hematopoiesis and, consequently, in haematological tumours. The researchers documented mutations of the RUNX1 gene in acute myeloid leukaemia (AML) [20], acute lymphoid leukaemia (ALL), and familial platelet disorder with a predisposition to acute myeloid leukaemia (FPD/AML). These mutations either influence or do not influence the binding ability of RUNX1 to the other target genes, with the more or less changed function, depending on the mutated region (DBD, TAD, or nuclear localisation domain).
RUNX1 expression changes are also found in solid tumours, like glioblastoma, ovarian, colon, breast, and hepatocellular carcinoma, where in tumour cells and available patient samples, it predominantly acts as a tumour suppressive. However, its oncogenic function is also documented [21][22][23][24][25][26].
RUNX2 is involved in the progression of various human tumours by regulating cell proliferation, angiogenesis, cancer stemness, and metastasis [27]. Its expression could be deregulated by several mechanisms. Recent research has uncovered numerous somatic mutations in the RUNX2 gene in various cancers, including missense, nonsense, and nonstop mutations and frameshift insertions and deletions [27].
RUNX3 is involved in carcinogenesis by interacting with several oncogenic signalling pathways, acting as a tumour suppressor in some tumours [28][29][30][31][32] and as an oncogene in others [33][34][35]. RUNX3 is frequently inactivated in human cancers by promoter DNA hypermethylation [28][29][30][31][32][36][37][38][39][40][41], histone modification [42][43], hemizygous deletion [38][39], and protein mislocalisation [6][31]. 

1.4. The Mechanisms of Action of RUNX Proteins

Also, the co-expression of RUNX genes with epigenetic regulators could affect the onset of some cancer types. Researchers should pay attention to epigenetic mechanisms of RUNX genes’ regulation, including DNA methylation and miRNAs [19]. As epigenetic regulators, RUNX proteins cooperate with diverse coregulators and involve many signal transduction processes. In addition, they participate in chromatin landscape remodelling [10]. There is evidence that RUNX proteins can function as pioneer transcription factors that recruit various chromatin remodelling enzymes and other transcription factors to open the condensed chromatin structure and thus activate the transcription of target genes [10][19][44]. This epigenetic role of RUNX genes appears to play a pivotal role in both physiological and pathological conditions, including cancer [10][19].

2. RUNX1 in HCC

2.1. RUNX1 Role in HCC

The role of RUNX1 in solid tumours is controversial, acting in two opposite ways. It can impede or promote carcinogenesis, as reviewed in [7][45]. Databases that collect transcriptomic studies and link data on the genomic and clinical parameters with various cancer groups show controversial results on the RUNX1 expression. According to the Gent2 and TIMER2.0 databases, there was a significantly higher expression of RUNX1 transcript in hepatocellular carcinoma compared to normal tissue [46][47]. However, the UCSC database shows the opposite results [48]. It has an upgraded version [49]. The RUNX1 expression was decreased in hepatocellular carcinoma. That was consistent with the work of Miyagawa and colleagues, who noticed that RUNX1 mRNA was 76% and 47% lower in HCC and cirrhotic tissue than in normal tissue. Also, there was a significant decrease in RUNX1 mRNA in HCC compared to cirrhotic liver samples [50].
One of the crucial processes in cancer progression is angiogenesis. In hematopoietic cell differentiation from hemogenic endothelium cells, RUNX1 has a vital role. The RUNX1-deficient mice lack hematopoiesis and angiogenesis [51]. Added exogenously, IGFBP-3 inhibited RUNX1-promoted angiogenesis dose-dependently [52]. Thus, it can conclude that RUNX1 has a cardinal role in angiogenic differentiation and vascularisation. Vascular endothelial growth factor (VEGF) is an angiogenesis modulator in a cancer cell environment and the negative prognostic factor for acute myeloid leukaemia. In the HCC cell culture, Elst and colleagues found that RUNX1 inhibited VEGF expression [53]. 

2.2. RUNX1 and miRNAs

There are not many studies of epigenetic processes involving the RUNX1 gene. Tuo and colleagues noticed the hypomethylation of the RUNX1 promoter in hepatocellular carcinoma [54]. Some studies show the association between several miRNAs and RUNX1 in HCC. Transcript 1 of RUNX1 (RUNX1-IT1) is a long non-coding sequence of an RNA transcript of the RUNX1 gene [55]. Yan and colleagues noticed the RUNX1 expression decrease in the HCC patients’ samples, and the knocking-down of RUNX1-IT1 increased the proliferation and reduced apoptosis in HCC cells [56]. Sun and colleagues observed the association of decreased RUNX1-IT1 expression with shorter DFS and OS. RUNX1-IT1 binds mir-632, competing with the other RNAs in HCC cells for target gene GSK-3β binding and modulating the WNT/β-catenin signalling cascade. Added hypoxia-prompted histone deacetylase 3 (HDAC3) in HCC cells reduced the RUNX1-IT1 expression. They concluded that the goal of HCC therapy should be to activate RUNX1-IT1 [57]. On the other hand, Vivacqua and colleagues noticed that oestrogen receptor agonists, such as the G protein-coupled oestrogen receptor agonist (G-1) and 17β-oestradiol (E2), increased miR-144 expression in HepG2 hepatocarcinoma cells, via the G protein-coupled oestrogen receptor 1 (GPER) and the PI3K/ERK1/2/Elk1 pathway. miR-144 then downregulates RUNX1, promoting the cell cycle [58].
In conclusion, RUNX1 binds target genes (VEGF and COL4A1) and involves signalling pathways of cancer proliferation, metastasis, and angiogenesis. RUNX1 also interacts with several miRNAs, for example, mir-632 and mir-144. Given the importance of RUNX1 in hepatocellular carcinoma, its potential suitability as a treatment target requires additional studies.

3. RUNX2 in HCC

3.1. General Role of RUNX2 in HCC

According to literature data, the expression of RUNX2 on mRNA and/or protein level is elevated in HCC cell lines, as well as in liver tumour tissue [59][60][61], suggesting that this transcription factor has a role in hepatocarcinogenesis. Previous findings confirmed higher RUNX2 expression in HCC patients than expression detected in non-tumour tissues or healthy controls [59][60][62]. Wang and colleagues noticed that increased expression of RUNX2 significantly correlates with unfavourable clinicopathological features in HCC. These adverse features included the onset of multiple tumour nodes, higher histological grades and TNM stages, and venous invasion presence [60].

3.2. RUNX2 Tumour Invasion Activity in HCC

The general mechanisms underlying the role of RUNX2 in various tumour types provide directions for detailed studies on the impact of RUNX2 on the pathogenesis of HCC. Many reports showed that increased RUNX2 expression enhances tumour cell migration and invasive properties [63][64][65][66][67][68][69]. Previous studies revealed the crucial role of the RUNX2 in the regulation of the epithelial-to-mesenchymal transition (EMT) process in many tumours [61][70], which is the first step toward tumour invasion and metastatic potential (Figure 2).
Cells 12 02303 g003
Figure 2. RUNX2 oncogenic mechanisms in hepatocellular carcinoma.

3.3. RUNX2 and Non-Coding RNAs in HCC

Previous studies showed that multiple microRNAs could be differentially expressed in HCC, directly or indirectly affecting RUNX2 expression and activity. RUNX2 might be directly repressed by the miR-455 molecule in human HCC samples [71], which has already demonstrated tumour-suppressive properties [72][73]. Further gain/loss-of-function analyses showed that in HCC cells, miR-455 regulates the process of RUNX2 accumulation in vitro, which significantly suppresses cell migration abilities [71]. Additionally, several miRNAs can regulate RUNX2 expression by directly binding to the RUNX2 gene 3′-UTR region [74][75]. Wang and colleagues suggested that miR-196a could have a significant role in HCC development through the RUNX2 upregulation, which in HCC cell lines produced higher osteopontin levels as a consequence [76]. Osteopontin is a well-known bone marrow-produced protein that regulates bone regeneration, although previous reports indicate that this protein also contributes to cancer metastasis [77].
RUNX2, a unique transcription factor, exhibits a crucial oncogenic role in hepatocellular carcinoma. Moreover, it should consider RUNX2 aberrant expression as a novel prognostic indicator in HCC. Studies on RUNX2-related regulatory mechanisms hint at its pro-invasive functions in HCC by reshaping the tumour microenvironment, making RUNX2 a potential therapeutic target for blocking metastasis and further disease progression. 

4. RUNX3 in HCC

4.1. General Role of RUNX3 in HCC

Several studies have shown that RUNX3 inactivation is cardinal for the initiation and progression of HCC [78][79][80][81][82][83]. As a multifunctional transcription factor, RUNX3 is implicated in diverse signalling pathways and cellular processes, thereby exerting multiple effects on tumour suppression [84][85]. According to current knowledge, RUNX3 participates in the regulation of the cell cycle [86], proliferation and apoptosis [87], angiogenesis [18], and EMT [78][88]. Its loss is also related to chemoresistance [89][90] (Figure 3).
Cells 12 02303 g004
Figure 3. The downregulation of RUNX3 in HCC.

4.2. RUNX3 Regulates Cell Cycle, Proliferation, and Apoptosis

Dysregulation of the cell cycle is a prime event in hepatocarcinogenesis. RUNX3 may play a pivotal role in this process by employing diverse mechanisms [87]. Earlier studies on gastric epithelial cells demonstrated that RUNX3 regulates the cell cycle by interacting with p21, p27, and cyclin D1 proteins [91][92][93]. Further research revealed that RUNX3 induces the expression of the ARF and CDKN1A cell cycle regulators by interaction with BRD2 and pRB proteins [28][86].
As the major component of the transforming growth factor-beta signalling (TGF-β) pathway [8][94], RUNX3 can stop cell proliferation, inducing a p21 cell-cycle inhibitor [93]. Similarly, it can suppress apoptosis by inducing apoptosis initiator Bim, as has been shown on gastric cancer cell lines [95].
Another study in mice showed that proliferation marker Ki67 was more frequently observed in the RUNX3 knockout liver cells than in wild-type cells, which further confirmed the role of RUNX3 in hepatocyte proliferation regulation [18]. RUNX3 has been reported to control cellular senescence, a potent anti-cancer mechanism that prevents the proliferation of potentially cancerous cells [96].
Oncogenic activation of the Notch signalling pathway is also implicated in hepatocyte growth and proliferation [97][98]. Gao and colleagues have shown that RUNX3 can suppress oncogenic Notch signalling through direct interaction with the intracellular domain of the Notch1 protein in HCC cell lines [85].

4.3. RUNX3 in the Angiogenesis Regulation

A crucial tumour-suppressive role of RUNX3 is angiogenesis prevention and tumour invasion. A recent study revealed that after the HCC therapeutic drug’s application, sorafenib, RUNX3 suppressed VEGF expression in HCC, which was associated with reduced tumour growth [99]. A previous study on gastric cancer cells demonstrated that RUNX3 destabilised hypoxia-inducible factor HIF-1α in the hypoxic microenvironment, thus inhibiting angiogenesis [100].

4.4. RUNX3 and Epithelial-Mesenchymal Transition

Previous studies have shown that the loss of RUNX3 contributes to EMT, a crucial process related to metastasis, chemoresistance, and tumour stemness [101][102]. In vitro experiments demonstrated that RUNX3 repressed tumour metastasis and invasion by upregulating E-cadherin through the miR-186/E-cadherin/EMT axis [78][103].

4.5. RUNX3 and Chemoresistance

A study on human HCC samples and cell lines demonstrated that RUNX3 could be downregulated by overexpression of miR-130 through the miR-130a/RUNX3/Wnt signalling pathway. This mechanism was associated with increased chemoresistance to cisplatin [90]. Studies in gastric [104] and cervical cancer [105] demonstrated that miR-130 directly binds to the RUNX3 and thus inhibits its expression. Accordingly, restoration of RUNX3 expression by targeting miR-130 could be a potential approach to overcome chemotherapy resistance in HCC patients.

5. Conclusions

Despite considerable advances in cancer diagnosis and treatment, HCC remains one of the most common and hard-to-treat human cancers. Revealing the essential molecular processes underlying hepatocarcinogenesis is crucial for establishing reliable diagnostic, prognostic, and therapeutic markers. RUNX genes are often deregulated in HCC, exerting complex and conflicting functions. The role of RUNX1 is still contradictory, as there are reports of its tumour-suppressive but also oncogenic role in HCC. According to current knowledge, RUNX2 acts as an oncogene and is related to the more aggressive forms of the disease, whereas RUNX3 exerts a tumour-suppressive role and could be used as a biomarker for early HCC detection. All three genes could serve as therapeutic targets. However, a deeper understanding of the relationship between different RUNX family members and the signalling pathways they are involved in, considering the cell-specific microenvironment, is necessary for effective HCC therapeutic strategy development.

Increasing evidence suggests that RUNX genes act as epigenetic modulators that interact with other chromatin landscape regulators to activate or repress the transcription of target genes [89]. Since normal epigenetic patterns are altered in all types of human cancers, it would be of great interest to investigate interactions between RUNX proteins and other epigenetic regulators, especially in HCC. This could potentially provide an avenue for epigenetic therapy.

References

  1. Asafo-Agyei, K.O.; Samant, H. Hepatocellular Carcinoma. In StatPearls; StatPearls Publishing: Treasure Islan, FL, USA, 2023.
  2. Llovet, J.M.; Kelley, R.K.; Villanueva, A.; Singal, A.G.; Pikarsky, E.; Roayaie, S.; Lencioni, R.; Koike, K.; Zucman-Rossi, J.; Finn, R.S. Hepatocellular Carcinoma. Nat. Rev. Dis. Prim. 2021, 7, 6.
  3. Balogh, J.; Victor, D.; Asham, E.H.; Burroughs, S.G.; Boktour, M.; Saharia, A.; Li, X.; Ghobrial, M.; Monsour, H. Hepatocellular Carcinoma: A Review. J. Hepatocell. Carcinoma 2016, 3, 41–53.
  4. Sim, H.-W.; Knox, J. Hepatocellular Carcinoma in the Era of Immunotherapy. Curr. Probl. Cancer 2018, 42, 40–48.
  5. Suresh, D.; Srinivas, A.N.; Prashant, A.; Harikumar, K.B.; Kumar, D.P. Therapeutic Options in Hepatocellular Carcinoma: A Comprehensive Review. Clin. Exp. Med. 2023.
  6. Chuang, L.S.H.; Ito, K.; Ito, Y. RUNX Family: Regulation and Diversification of Roles through Interacting Proteins. Int. J. Cancer 2013, 132, 1260–1271.
  7. Otálora-Otálora, B.A.; Henríquez, B.; López-Kleine, L.; Rojas, A. RUNX Family: Oncogenes or Tumor Suppressors (Review). Oncol. Rep. 2019, 42, 3–19.
  8. Ito, Y.; Bae, S.-C.; Chuang, L.S.H. The RUNX Family: Developmental Regulators in Cancer. Nat. Rev. Cancer 2015, 15, 81–95.
  9. Levanon, D.; Groner, Y. Structure and Regulated Expression of Mammalian RUNX Genes. Oncogene 2004, 23, 4211–4219.
  10. Yi, H.; He, Y.; Zhu, Q.; Fang, L. RUNX Proteins as Epigenetic Modulators in Cancer. Cells 2022, 11, 3687.
  11. Mevel, R.; Draper, J.E.; Lie-a-Ling, M.; Kouskoff, V.; Lacaud, G. RUNX Transcription Factors: Orchestrators of Development. Development 2019, 146, dev148296.
  12. Darnell, J.E. Transcription Factors as Targets for Cancer Therapy. Nat. Rev. Cancer 2002, 2, 740–749.
  13. Ito, Y. Oncogenic Potential of the RUNX Gene Family: ‘Overview’. Oncogene 2004, 23, 4198–4208.
  14. Lee, Y.M. RUNX Family in Hypoxic Microenvironment and Angiogenesis in Cancers. Cells 2022, 11, 3098.
  15. Sood, R.; Kamikubo, Y.; Liu, P. Role of RUNX1 in Hematological Malignancies. Blood 2017, 129, 2070–2082.
  16. Yamagata, T.; Maki, K.; Mitani, K. Runx1/AML1 in Normal and Abnormal Hematopoiesis. Int. J. Hematol. 2005, 82, 1–8.
  17. Dalle Carbonare, L.; Innamorati, G.; Valenti, M.T. Transcription Factor Runx2 and Its Application to Bone Tissue Engineering. Stem Cell Rev. Rep. 2012, 8, 891–897.
  18. Lee, J.-M.; Lee, D.-J.; Bae, S.-C.; Jung, H.-S. Abnormal Liver Differentiation and Excessive Angiogenesis in Mice Lacking Runx3. Histochem. Cell Biol. 2013, 139, 751–758.
  19. Pan, S.; Sun, S.; Liu, B.; Hou, Y. Pan-Cancer Landscape of the RUNX Protein Family Reveals Their Potential as Carcinogenic Biomarkers and the Mechanisms Underlying Their Action. J. Transl. Intern. Med. 2022, 10, 156–174.
  20. Papaemmanuil, E.; Gerstung, M.; Bullinger, L.; Gaidzik, V.I.; Paschka, P.; Roberts, N.D.; Potter, N.E.; Heuser, M.; Thol, F.; Bolli, N.; et al. Genomic Classification and Prognosis in Acute Myeloid Leukemia. N. Engl. J. Med. 2016, 374, 2209–2221.
  21. Keita, M.; Bachvarova, M.; Morin, C.; Plante, M.; Gregoire, J.; Renaud, M.-C.; Sebastianelli, A.; Trinh, X.B.; Bachvarov, D. The RUNX1 Transcription Factor Is Expressed in Serous Epithelial Ovarian Carcinoma and Contributes to Cell Proliferation, Migration and Invasion. Cell Cycle 2013, 12, 972–986.
  22. Liu, C.; Xu, D.; Xue, B.; Liu, B.; Li, J.; Huang, J. Upregulation of RUNX1 Suppresses Proliferation and Migration through Repressing VEGFA Expression in Hepatocellular Carcinoma. Pathol. Oncol. Res. 2020, 26, 1301–1311.
  23. Li, Q.; Lai, Q.; He, C.; Fang, Y.; Yan, Q.; Zhang, Y.; Wang, X.; Gu, C.; Wang, Y.; Ye, L.; et al. RUNX1 Promotes Tumour Metastasis by Activating the Wnt/β-Catenin Signalling Pathway and EMT in Colorectal Cancer. J. Exp. Clin. Cancer Res. 2019, 38, 334.
  24. Lu, C.; Yang, Z.; Yu, D.; Lin, J.; Cai, W. RUNX1 Regulates TGF-β Induced Migration and EMT in Colorectal Cancer. Pathol. Res. Pract. 2020, 216, 153142.
  25. Sangpairoj, K.; Vivithanaporn, P.; Apisawetakan, S.; Chongthammakun, S.; Sobhon, P.; Chaithirayanon, K. RUNX1 Regulates Migration, Invasion, and Angiogenesis via P38 MAPK Pathway in Human Glioblastoma. Cell. Mol. Neurobiol. 2017, 37, 1243–1255.
  26. Fritz, A.J.; Hong, D.; Boyd, J.; Kost, J.; Finstaad, K.H.; Fitzgerald, M.P.; Hanna, S.; Abuarqoub, A.H.; Malik, M.; Bushweller, J.; et al. RUNX1 and RUNX2 Transcription Factors Function in Opposing Roles to Regulate Breast Cancer Stem Cells. J. Cell. Physiol. 2020, 235, 7261–7272.
  27. Lin, T.-C. RUNX2 and Cancer. Int. J. Mol. Sci. 2023, 24, 7001.
  28. Lee, Y.-S.; Lee, J.-W.; Jang, J.-W.; Chi, X.-Z.; Kim, J.-H.; Li, Y.-H.; Kim, M.-K.; Kim, D.-M.; Choi, B.-S.; Kim, E.-G.; et al. Runx3 Inactivation Is a Crucial Early Event in the Development of Lung Adenocarcinoma. Cancer Cell 2013, 24, 603–616.
  29. Li, Q.-L.; Ito, K.; Sakakura, C.; Fukamachi, H.; Inoue, K.; Chi, X.-Z.; Lee, K.-Y.; Nomura, S.; Lee, C.-W.; Han, S.-B.; et al. Causal Relationship between the Loss of RUNX3 Expression and Gastric Cancer. Cell 2002, 109, 113–124.
  30. Goel, A.; Arnold, C.N.; Tassone, P.; Chang, D.K.; Niedzwiecki, D.; Dowell, J.M.; Wasserman, L.; Compton, C.; Mayer, R.J.; Bertagnolli, M.M.; et al. Epigenetic Inactivation OfRUNX3 in Microsatellite Unstable Sporadic Colon Cancers. Int. J. Cancer 2004, 112, 754–759.
  31. Kang, G.H.; Lee, S.; Lee, H.J.; Hwang, K.S. Aberrant CpG Island Hypermethylation of Multiple Genes in Prostate Cancer and Prostatic Intraepithelial Neoplasia: CpG Island Methylation in Prostate Cancer and PIN. J. Pathol. 2004, 202, 233–240.
  32. Lau, Q.C.; Raja, E.; Salto-Tellez, M.; Liu, Q.; Ito, K.; Inoue, M.; Putti, T.C.; Loh, M.; Ko, T.K.; Huang, C.; et al. RUNX3 Is Frequently Inactivated by Dual Mechanisms of Protein Mislocalization and Promoter Hypermethylation in Breast Cancer. Cancer Res. 2006, 66, 6512–6520.
  33. Tsunematsu, T.; Kudo, Y.; Iizuka, S.; Ogawa, I.; Fujita, T.; Kurihara, H.; Abiko, Y.; Takata, T. RUNX3 Has an Oncogenic Role in Head and Neck Cancer. PLoS ONE 2009, 4, e5892.
  34. Zhang, Z.; Chen, G.; Cheng, Y.; Martinka, M.; Li, G. Prognostic Significance of RUNX3 Expression in Human Melanoma: RUNX3 in Melanoma Prognosis. Cancer 2011, 117, 2719–2727.
  35. Nevadunsky, N.S.; Barbieri, J.S.; Kwong, J.; Merritt, M.A.; Welch, W.R.; Berkowitz, R.S.; Mok, S.C. RUNX3 Protein Is Overexpressed in Human Epithelial Ovarian Cancer. Gynecol. Oncol. 2009, 112, 325–330.
  36. Kim, W.-J.; Kim, E.-J.; Jeong, P.; Quan, C.; Kim, J.; Li, Q.-L.; Yang, J.-O.; Ito, Y.; Bae, S.-C. RUNX3 Inactivation by Point Mutations and Aberrant DNA Methylation in Bladder Tumors. Cancer Res. 2005, 65, 9347–9354.
  37. Lund, A.H.; Van Lohuizen, M. RUNX: A Trilogy of Cancer Genes. Cancer Cell 2002, 1, 213–215.
  38. Nakanishi, Y.; Shiraha, H.; Nishina, S.; Tanaka, S.; Matsubara, M.; Horiguchi, S.; Iwamuro, M.; Takaoka, N.; Uemura, M.; Kuwaki, K.; et al. Loss of Runt-Related Transcription Factor 3 Expression Leads Hepatocellular Carcinoma Cells to Escape Apoptosis. BMC Cancer 2011, 11, 3.
  39. Mori, T.; Nomoto, S.; Koshikawa, K.; Fujii, T.; Sakai, M.; Nishikawa, Y.; Inoue, S.; Takeda, S.; Kaneko, T.; Nakao, A. Decreased Expression and Frequent Allelic Inactivation of the RUNX3 Gene at 1p36 in Human Hepatocellular Carcinoma. Liver Int. 2005, 25, 380–388.
  40. Steinhart, Z.; Angers, S. Wnt Signaling in Development and Tissue Homeostasis. Development 2018, 145, dev146589.
  41. Ito, K.; Lim, A.C.-B.; Salto-Tellez, M.; Motoda, L.; Osato, M.; Chuang, L.S.H.; Lee, C.W.L.; Voon, D.C.-C.; Koo, J.K.W.; Wang, H.; et al. RUNX3 Attenuates β-Catenin/T Cell Factors in Intestinal Tumorigenesis. Cancer Cell 2008, 14, 226–237.
  42. Lee, Y.M. Control of RUNX3 by Histone Methyltransferases. J. Cell. Biochem. 2011, 112, 394–400.
  43. Lee, S.H.; Kim, J.; Kim, W.-H.; Lee, Y.M. Hypoxic Silencing of Tumor Suppressor RUNX3 by Histone Modification in Gastric Cancer Cells. Oncogene 2009, 28, 184–194.
  44. Zaret, K.S.; Carroll, J.S. Pioneer Transcription Factors: Establishing Competence for Gene Expression. Genes Dev. 2011, 25, 2227–2241.
  45. Lin, T.-C. RUNX1 and Cancer. Biochim. Biophys. Acta (BBA) Rev. Cancer 2022, 1877, 188715.
  46. TIMER2.0. Available online: http://timer.cistrome.org/ (accessed on 3 April 2023).
  47. GENT2. Available online: http://gent2.appex.kr/gent2/ (accessed on 3 April 2023).
  48. Zhu, J.; Sanborn, J.Z.; Benz, S.; Szeto, C.; Hsu, F.; Kuhn, R.M.; Karolchik, D.; Archie, J.; Lenburg, M.E.; Esserman, L.J.; et al. The UCSC Cancer Genomics Browser. Nat. Methods 2009, 6, 239–240.
  49. UCSC Xena. Available online: http://xena.ucsc.edu/welcome-to-ucsc-xena/ (accessed on 3 April 2023).
  50. Miyagawa, K.; Sakakura, C.; Nakashima, S.; Yoshikawa, T.; Kin, S.; Nakase, Y.; Ito, K.; Yamagishi, H.; Ida, H.; Yazumi, S.; et al. Down-Regulation of RUNX1, RUNX3 and CBFbeta in Hepatocellular Carcinomas in an Early Stage of Hepatocarcinogenesis. Anticancer Res. 2006, 26, 3633–3643.
  51. Takakura, N.; Watanabe, T.; Suenobu, S.; Yamada, Y.; Noda, T.; Ito, Y.; Satake, M.; Suda, T. A Role for Hematopoietic Stem Cells in Promoting Angiogenesis. Cell 2000, 102, 199–209.
  52. Iwatsuki, K.; Tanaka, K.; Kaneko, T.; Kazama, R.; Okamoto, S.; Nakayama, Y.; Ito, Y.; Satake, M.; Takahashi, S.-I.; Miyajima, A.; et al. Runx1 Promotes Angiogenesis by Downregulation of Insulin-like Growth Factor-Binding Protein-3. Oncogene 2005, 24, 1129–1137.
  53. Ter Elst, A.; Ma, B.; Scherpen, F.J.G.; De Jonge, H.J.M.; Douwes, J.; Wierenga, A.T.J.; Schuringa, J.J.; Kamps, W.A.; De Bont, E.S.J.M. Repression of Vascular Endothelial Growth Factor Expression by the Runt-Related Transcription Factor 1 in Acute Myeloid Leukemia. Cancer Res. 2011, 71, 2761–2771.
  54. Tuo, Z.; Zhang, Y.; Wang, X.; Dai, S.; Liu, K.; Xia, D.; Wang, J.; Bi, L. RUNX1 Is a Promising Prognostic Biomarker and Related to Immune Infiltrates of Cancer-Associated Fibroblasts in Human Cancers. BMC Cancer 2022, 22, 523.
  55. National Library of Medicine. RUNX1-IT1 RUNX1 Intronic Transcript 1 . Available online: https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=DetailsSearch&Term=80215 (accessed on 18 March 2023).
  56. Yan, P.-H.; Wang, L.; Chen, H.; Yu, F.-Q.; Guo, L.; Liu, Y.; Zhang, W.-J.; Bai, Y.-L. LncRNA RUNX1-IT1 Inhibits Proliferation and Promotes Apoptosis of Hepatocellular Carcinoma by Regulating MAPK Pathways. Eur. Rev. Med. Pharmacol. Sci. 2019, 23, 8287–8294.
  57. Sun, L.; Wang, L.; Chen, T.; Shi, Y.; Yao, B.; Liu, Z.; Wang, Y.; Li, Q.; Liu, R.; Niu, Y.; et al. LncRNA RUNX1-IT1 Which Is Downregulated by Hypoxia-Driven Histone Deacetylase 3 Represses Proliferation and Cancer Stem-like Properties in Hepatocellular Carcinoma Cells. Cell Death Dis. 2020, 11, 95.
  58. Vivacqua, A.; De Marco, P.; Santolla, M.F.; Cirillo, F.; Pellegrino, M.; Panno, M.L.; Abonante, S.; Maggiolini, M. Estrogenic Gper Signaling Regulates Mir144 Expression in Cancer Cells and Cancer-Associated Fibroblasts (Cafs). Oncotarget 2015, 6, 16573–16587.
  59. Jing, G.; Zheng, X.; Ji, X. LncRNA HAND2-AS1 Overexpression Inhibits Cancer Cell Proliferation in Hepatocellular Carcinoma by Downregulating RUNX2 Expression. J. Clin. Lab. Anal. 2021, 35, e23717.
  60. Wang, Q.; Yu, W.; Huang, T.; Zhu, Y.; Huang, C. RUNX2 Promotes Hepatocellular Carcinoma Cell Migration and Invasion by Upregulating MMP9 Expression. Oncol. Rep. 2016, 36, 2777–2784.
  61. Cao, Z.; Sun, B.; Zhao, X.; Zhang, Y.; Gu, Q.; Liang, X.; Dong, X.; Zhao, N. Correction: Cao, Z.; et al. The Expression and Functional Significance of Runx2 in Hepatocellular Carcinoma: Its Role in Vasculogenic Mimicry and Epithelial—Mesenchymal Transition. Int. J. Mol. Sci. 2020, 18, 500.
  62. Emma, M.R.; Iovanna, J.L.; Bachvarov, D.; Puleio, R.; Loria, G.R.; Augello, G.; Candido, S.; Libra, M.; Gulino, A.; Cancila, V.; et al. NUPR1, a New Target in Liver Cancer: Implication in Controlling Cell Growth, Migration, Invasion and Sorafenib Resistance. Cell Death Dis. 2016, 7, e2269.
  63. Wang, X.; Li, L.; Wu, Y.; Zhang, R.; Zhang, M.; Liao, D.; Wang, G.; Qin, G.; Xu, R.; Kang, T. CBX4 Suppresses Metastasis via Recruitment of HDAC3 to the Runx2 Promoter in Colorectal Carcinoma. Cancer Res. 2016, 76, 7277–7289.
  64. Sase, T.; Suzuki, T.; Miura, K.; Shiiba, K.; Sato, I.; Nakamura, Y.; Takagi, K.; Onodera, Y.; Miki, Y.; Watanabe, M.; et al. Runt-Related Transcription Factor 2 in Human Colon Carcinoma: A Potent Prognostic Factor Associated with Estrogen Receptor. Int. J. Cancer 2012, 131, 2284–2293.
  65. Komori, T. Runx2, A Multifunctional Transcription Factor in Skeletal Development. J. Cell. Biochem. 2002, 87, 1–8.
  66. Pratap, J.; Javed, A.; Languino, L.R.; Van Wijnen, A.J.; Stein, J.L.; Stein, G.S.; Lian, J.B. The Runx2 Osteogenic Transcription Factor Regulates Matrix Metalloproteinase 9 in Bone Metastatic Cancer Cells and Controls Cell Invasion. Mol. Cell. Biol. 2005, 25, 8581–8591.
  67. Boregowda, R.K.; Olabisi, O.O.; Abushahba, W.; Jeong, B.-S.; Haenssen, K.K.; Chen, W.; Chekmareva, M.; Lasfar, A.; Foran, D.J.; Goydos, J.S.; et al. RUNX2 Is Overexpressed in Melanoma Cells and Mediates Their Migration and Invasion. Cancer Lett. 2014, 348, 61–70.
  68. Li, X.-Q.; Du, X.; Li, D.-M.; Kong, P.-Z.; Sun, Y.; Liu, P.-F.; Wang, Q.-S.; Feng, Y.-M. ITGBL1 Is a Runx2 Transcriptional Target and Promotes Breast Cancer Bone Metastasis by Activating the TGFβ Signaling Pathway. Cancer Res. 2015, 75, 3302–3313.
  69. El-Gendi, S.M.; Mostafa, M.F. Runx2 Expression as a Potential Prognostic Marker in Invasive Ductal Breast Carcinoma. Pathol. Oncol. Res. 2016, 22, 461–470.
  70. Baniwal, S.K.; Khalid, O.; Gabet, Y.; Shah, R.R.; Purcell, D.J.; Mav, D.; Kohn-Gabet, A.E.; Shi, Y.; Coetzee, G.A.; Frenkel, B. Runx2 Transcriptome of Prostate Cancer Cells: Insights into Invasiveness and Bone Metastasis. Mol. Cancer 2010, 9, 258.
  71. Qin, L.; Zhang, Y.; Lin, J.; Shentu, Y.; Xie, X. MicroRNA-455 Regulates Migration and Invasion of Human Hepatocellular Carcinoma by Targeting Runx2. Oncol. Rep. 2016, 36, 3325–3332.
  72. Li, Y.-J.; Ping, C.; Tang, J.; Zhang, W. MicroRNA-455 Suppresses Non-Small Cell Lung Cancer through Targeting ZEB1: The Role of MiRNA-455 in NSCLC. Cell Biol. Int. 2016, 40, 621–628.
  73. Chai, J.; Wang, S.; Han, D.; Dong, W.; Xie, C.; Guo, H. MicroRNA-455 Inhibits Proliferation and Invasion of Colorectal Cancer by Targeting RAF Proto-Oncogene Serine/Threonine-Protein Kinase. Tumor Biol. 2015, 36, 1313–1321.
  74. Chou, C.-H.; Shrestha, S.; Yang, C.-D.; Chang, N.-W.; Lin, Y.-L.; Liao, K.-W.; Huang, W.-C.; Sun, T.-H.; Tu, S.-J.; Lee, W.-H.; et al. MiRTarBase Update 2018: A Resource for Experimentally Validated MicroRNA-Target Interactions. Nucleic Acids Res. 2018, 46, D296–D302.
  75. Zhao, W.; Zhang, S.; Wang, B.; Huang, J.; Lu, W.W.; Chen, D. Runx2 and MicroRNA Regulation in Bone and Cartilage Diseases: Runx2 and MiRNAs in Bone and Cartilage. Ann. N. Y. Acad. Sci. 2016, 1383, 80–87.
  76. Wang, S.-Y.; Chen, C.-L.; Hu, Y.-C.; Chi, Y.; Huang, Y.-H.; Su, C.-W.; Jeng, W.-J.; Liang, Y.-J.; Wu, J.-C. High Expression of MicroRNA-196a Is Associated with Progression of Hepatocellular Carcinoma in Younger Patients. Cancers 2019, 11, 1549.
  77. Wai, P.Y.; Kuo, P.C. The Role of Osteopontin in Tumor Metastasis. J. Surg. Res. 2004, 121, 228–241.
  78. Gou, Y.; Zhai, F.; Zhang, L.; Cui, L. RUNX3 Regulates Hepatocellular Carcinoma Cell Metastasis via Targeting MiR-186/E-Cadherin/EMT Pathway. Oncotarget 2017, 8, 61475–61486.
  79. Zhang, X.; He, H.; Zhang, X.; Guo, W.; Wang, Y. RUNX3 Promoter Methylation Is Associated with Hepatocellular Carcinoma Risk: A Meta-Analysis. Cancer Investig. 2015, 33, 121–125.
  80. Yang, Y.; Ye, Z.; Zou, Z.; Xiao, G.; Luo, G.; Yang, H. Clinicopathological Significance of RUNX3 Gene Hypermethylation in Hepatocellular Carcinoma. Tumor Biol. 2014, 35, 10333–10340.
  81. El-shaarawy, F.; Abo ElAzm, M.M.; Mohamed, R.H.; Radwan, M.I.; Abo-Elmatty, D.M.; Mehanna, E.T. Relation of the Methylation State of RUNX3 and P16 Gene Promoters with Hepatocellular Carcinoma in Egyptian Patients. Egypt. J. Med. Hum. Genet. 2022, 23, 48.
  82. Sun, G.; Zhang, C.; Feng, M.; Liu, W.; Xie, H.; Qin, Q.; Zhao, E.; Wan, L. Methylation Analysis of P16, SLIT2, SCARA5, and Runx3 Genes in Hepatocellular Carcinoma. Medicine 2017, 96, e8279.
  83. El-Bendary, M.; Nour, D.; Arafa, M.; Neamatallah, M. Methylation of Tumour Suppressor Genes RUNX3, RASSF1A and E-Cadherin in HCV-Related Liver Cirrhosis and Hepatocellular Carcinoma. Br. J. Biomed. Sci. 2020, 77, 35–40.
  84. Chen, F.; Liu, X.; Bai, J.; Pei, D.; Zheng, J. The Emerging Role of RUNX3 in Cancer Metastasis (Review). Oncol. Rep. 2016, 35, 1227–1236.
  85. Gao, J.; Chen, Y.; Wu, K.-C.; Liu, J.; Zhao, Y.-Q.; Pan, Y.-L.; Du, R.; Zheng, G.-R.; Xiong, Y.-M.; Xu, H.-L.; et al. RUNX3 Directly Interacts with Intracellular Domain of Notch1 and Suppresses Notch Signaling in Hepatocellular Carcinoma Cells. Exp. Cell Res. 2010, 316, 149–157.
  86. Chi, X.-Z.; Lee, J.-W.; Lee, Y.-S.; Park, I.Y.; Ito, Y.; Bae, S.-C. Runx3 Plays a Critical Role in Restriction-Point and Defense against Cellular Transformation. Oncogene 2017, 36, 6884–6894.
  87. Shiraha, H.; Nishina, S.; Yamamoto, K. Loss of Runt-Related Transcription Factor 3 Causes Development and Progression of Hepatocellular Carcinoma. J. Cell. Biochem. 2011, 112, 745–749.
  88. Tanaka, S.; Shiraha, H.; Nakanishi, Y.; Nishina, S.-I.; Matsubara, M.; Horiguchi, S.; Takaoka, N.; Iwamuro, M.; Kataoka, J.; Kuwaki, K.; et al. Runt-Related Transcription Factor 3 Reverses Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma. Int. J. Cancer 2012, 131, 2537–2546.
  89. Kataoka, J.; Shiraha, H.; Horiguchi, S.; Sawahara, H.; Uchida, D.; Nagahara, T.; Iwamuro, M.; Morimoto, H.; Takeuchi, Y.; Kuwaki, K.; et al. Loss of Runt-Related Transcription Factor 3 Induces Resistance to 5-Fluorouracil and Cisplatin in Hepatocellular Carcinoma. Oncol. Rep. 2016, 35, 2576–2582.
  90. Xu, N.; Shen, C.; Luo, Y.; Xia, L.; Xue, F.; Xia, Q.; Zhang, J. Upregulated MiR-130a Increases Drug Resistance by Regulating RUNX3 and Wnt Signaling in Cisplatin-Treated HCC Cell. Biochem. Biophys. Res. Commun. 2012, 425, 468–472.
  91. Chen, W.; Gao, N.; Shen, Y.; Cen, J. Hypermethylation Downregulates Runx3 Gene Expression and Its Restoration Suppresses Gastric Epithelial Cell Growth by Inducing P27 and Caspase3 in Human Gastric Cancer. J. Gastroenterol. Hepatol. 2010, 25, 823–831.
  92. Wei, D.; Gong, W.; Oh, S.C.; Li, Q.; Kim, W.D.; Wang, L.; Le, X.; Yao, J.; Wu, T.T.; Huang, S.; et al. Loss of RUNX3 Expression Significantly Affects the Clinical Outcome of Gastric Cancer Patients and Its Restoration Causes Drastic Suppression of Tumor Growth and Metastasis. Cancer Res. 2005, 65, 4809–4816.
  93. Chi, X.-Z.; Yang, J.-O.; Lee, K.-Y.; Ito, K.; Sakakura, C.; Li, Q.-L.; Kim, H.-R.; Cha, E.-J.; Lee, Y.-H.; Kaneda, A.; et al. RUNX3 Suppresses Gastric Epithelial Cell Growth by Inducing P21WAF1/Cip1 Expression in Cooperation with Transforming Growth Factor β-Activated SMAD. Mol. Cell. Biol. 2005, 25, 8097–8107.
  94. Ito, Y.; Miyazono, K. RUNX Transcription Factors as Key Targets of TGF-β Superfamily Signaling. Curr. Opin. Genet. Dev. 2003, 13, 43–47.
  95. Yano, T.; Ito, K.; Fukamachi, H.; Chi, X.-Z.; Wee, H.-J.; Inoue, K.; Ida, H.; Bouillet, P.; Strasser, A.; Bae, S.-C.; et al. The RUNX3 Tumor Suppressor Upregulates Bim in Gastric Epithelial Cells Undergoing Transforming Growth Factorβ-Induced Apoptosis. Mol. Cell. Biol. 2006, 26, 4474–4488.
  96. Zeng, S.; Shen, W.; Liu, L. Senescence and Cancer. Cancer Transl. Med. 2018, 4, 70.
  97. Giovannini, C.; Fornari, F.; Piscaglia, F.; Gramantieri, L. Notch Signaling Regulation in HCC: From Hepatitis Virus to Non-Coding RNAs. Cells 2021, 10, 521.
  98. Ahn, S.; Hyeon, J.; Park, C.-K. Notchl and Notch4 Are Markers for Poor Prognosis of Hepatocellular Carcinoma. Hepatobiliary Pancreat. Dis. Int. 2013, 12, 286–294.
  99. Chai, M.Y.; Kou, B.X.; Fu, Z.; Wei, F.L.; Dou, S.S.; Chen, D.X.; Liu, X.N. Sorafenib regulates vascular endothelial growth factor by runt-related transcription factor-3 to inhibit angiogenesis in hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi 2022, 30, 770–776.
  100. Lee, S.H.; Bae, S.C.; Kim, K.W.; Lee, Y.M. RUNX3 Inhibits Hypoxia-Inducible Factor-1α Protein Stability by Interacting with Prolyl Hydroxylases in Gastric Cancer Cells. Oncogene 2014, 33, 1458–1467.
  101. Lamouille, S.; Xu, J.; Derynck, R. Molecular Mechanisms of Epithelial–Mesenchymal Transition. Nat. Rev. Mol. Cell Biol. 2014, 15, 178–196.
  102. Voon, D.C.-C.; Wang, H.; Koo, J.K.W.; Nguyen, T.A.P.; Hor, Y.T.; Chu, Y.-S.; Ito, K.; Fukamachi, H.; Chan, S.L.; Thiery, J.P.; et al. Runx3 Protects Gastric Epithelial Cells Against Epithelial-Mesenchymal Transition-Induced Cellular Plasticity and Tumorigenicity. Stem Cells 2012, 30, 2088–2099.
  103. Loh, C.-Y.; Chai, J.; Tang, T.; Wong, W.; Sethi, G.; Shanmugam, M.; Chong, P.; Looi, C. The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges. Cells 2019, 8, 1118.
  104. Lee, S.H.; Jung, Y.D.; Choi, Y.S.; Lee, Y.M. Targeting of RUNX3 by MiR-130a and MiR-495 Cooperatively Increases Cell Proliferation and Tumor Angiogenesis in Gastric Cancer Cells. Oncotarget 2015, 6, 33269–33278.
  105. Wang, M.; Wang, X.; Liu, W. MicroRNA-130a-3p Promotes the Proliferation and Inhibits the Apoptosis of Cervical Cancer Cells via Negative Regulation of RUNX3. Mol. Med. Rep. 2020, 22, 2990–3000.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Biochemistry & Molecular Biology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Milena Krajnović
,
Bojana Kožik
,
Ana Božović
,
Snežana Jovanović-Ćupić
View Times: 157
Revisions: 2 times (View History)
Update Date: 24 Nov 2023
Table of Contents
    1000/1000
    Hot Most Recent
    ScholarVision Creations
    Feedback