miR-4319 Suppresses the Growth of Esophageal Squamous Cell Carcinoma Via Targeting NLRC5

Author(s): Xiao Hu, Min Wang, Lei Cao, Li Cong, Yujie Gao, Jianwei Lu, Jifeng Feng, Bo Shen, Delin Liu*

Journal Name: Current Molecular Pharmacology

Volume 13 , Issue 2 , 2020

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Graphical Abstract:


Background: The functions of microRNAs (miRNAs) in cancer progression have been recognized in recent years. However, the role of miR-4319 in esophageal squamous cell carcinoma (ESCC) remains unclear.

Objective: We aimed to investigate the biological roles of miR-4319 in ESCC progression and the associated mechanisms.

Methods: Real-time PCR was performed to examine the levels of miR-4319 in ESCC cell lines. The effects of miR-4319 and NOD-like receptor (NLR) family, caspase activation and recruitment domain (CARD) domain containing 5 (NLRC5) on cell proliferation and cell cycle progression were evaluated using MTT assay, colony formation and flow cytometry assays. Bioinformatics techniques and luciferase reporter assay were applied to validate NLRC5 as a miR-4319 target.

Results: The miR-4319 expression was lower in ESCC cells than in the normal cell line. The expression of miR-4319 repressed cell growth and induced cell cycle arrest. NLRC5 was validated as a direct downstream target of miR-4319. Overexpression of NLRC5 potentiated the effects of miR-4319 on cell growth and cell cycle distribution.

Conclusion: Our results demonstrated that miR-4319 might function as a tumor suppressor by targeting NLRC5 in ESCC.

Keywords: miR-4319, NLRC5, esophageal squamous cell carcinoma, cell growth, cell cycle, cell culture.

Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
Rustgi, A.K.; El-Serag, H.B. Esophageal carcinoma. N. Engl. J. Med., 2014, 371(26), 2499-2509.
[http://dx.doi.org/10.1056/NEJMra1314530] [PMID: 25539106]
Kim, T.; Grobmyer, S.R.; Smith, R.; Ben-David, K.; Ang, D.; Vogel, S.B.; Hochwald, S.N. Esophageal cancer--the five year survivors. J. Surg. Oncol., 2011, 103(2), 179-183.
[http://dx.doi.org/10.1002/jso.21784] [PMID: 21259254]
Kaikkonen, M.U.; Adelman, K. Emerging Roles of Non-Coding RNA Transcription. Trends Biochem. Sci., 2018, 43(9), 654-667.
[http://dx.doi.org/10.1016/j.tibs.2018.06.002] [PMID: 30145998]
Tang, D.; Zhao, X.; Zhang, L.; Wang, Z.; Wang, C. Identification of hub genes to regulate breast cancer metastasis to brain by bioinformatics analyses. J. Cell. Biochem., 2019, 120(6), 9522-9531.
[http://dx.doi.org/10.1002/jcb.28228] [PMID: 30506958]
Zhao, X.; Tang, D.Y.; Zuo, X.; Zhang, T.D.; Wang, C. Identification of lncRNA-miRNA-mRNA regulatory network associated with epithelial ovarian cancer cisplatin-resistant. J. Cell. Physiol., 2019, 234(11), 19886-19894.
[http://dx.doi.org/10.1002/jcp.28587] [PMID: 30950060]
Bartel, D.P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 2004, 116(2), 281-297.
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438]
Zheng, S.; Liu, Q.; Ma, R.; Tan, D.; Shen, T.; Zhang, X.; Lu, X. Let-7b-5p inhibits proliferation and motility in squamous cell carcinoma cells through negative modulation of KIAA1377. Cell Biol. Int., 2019, 43(6), 634-641.
[http://dx.doi.org/10.1002/cbin.11136] [PMID: 30958603]
Qiao, G.; Dai, C.; He, Y.; Shi, J.; Xu, C. Effects of miR‑106b‑3p on cell proliferation and epithelial‑mesenchymal transition, and targeting of ZNRF3 in esophageal squamous cell carcinoma. Int. J. Mol. Med., 2019, 43(4), 1817-1829.
[http://dx.doi.org/10.3892/ijmm.2019.4107] [PMID: 30816445]
Huang, L.; Zhang, Y.; Li, Z.; Zhao, X.; Xi, Z.; Chen, H.; Shi, H.; Xin, T.; Shen, R.; Wang, T. MiR-4319 suppresses colorectal cancer progression by targeting ABTB1. United European Gastroenterol. J., 2019, 7(4), 517-528.
[http://dx.doi.org/10.1177/2050640619837440] [PMID: 31065369]
Yang, Y.; Li, H.; Liu, Y.; Chi, C.; Ni, J.; Lin, X. MiR-4319 hinders YAP expression to restrain non-small cell lung cancer growth through regulation of LIN28-mediated RFX5 stability. Biomed. Pharmacother., 2019, 115 108956
[http://dx.doi.org/10.1016/j.biopha.2019.108956] [PMID: 31096145]
Lin, X.; Wang, Y. Re-expression of microRNA-4319 inhibits growth of prostate cancer via Her-2 suppression. Clin. Transl. Oncol., 2018, 20(11), 1400-1407.
[http://dx.doi.org/10.1007/s12094-018-1871-y] [PMID: 29633185]
Bian, S. miR-4319 inhibited the development of thyroid cancer by modulating FUS-stabilized SMURF1. J. Cell. Biochem., 2019.
[http://dx.doi.org/10.1002/jcb.29026] [PMID: 31148243]
Yoshihama, S.; Vijayan, S.; Sidiq, T.; Kobayashi, K.S. NLRC5/CITA: A Key Player in Cancer Immune Surveillance. Trends Cancer, 2017, 3(1), 28-38.
[http://dx.doi.org/10.1016/j.trecan.2016.12.003] [PMID: 28718425]
Li, Y.; Zhang, M.; Zheng, X. High Expression of NLRC5 Is Associated with Prognosis of Gastric Cancer. Open Med. (Wars.), 2018, 13, 443-449.
[http://dx.doi.org/10.1515/med-2018-0066] [PMID: 30426081]
Wang, Q.; Ding, H.; He, Y.; Li, X.; Cheng, Y.; Xu, Q.; Yang, Y.; Liao, G.; Meng, X.; Huang, C.; Li, J. NLRC5 mediates cell proliferation, migration, and invasion by regulating the Wnt/β-catenin signalling pathway in clear cell renal cell carcinoma. Cancer Lett., 2019, 444, 9-19.
[http://dx.doi.org/10.1016/j.canlet.2018.11.024] [PMID: 30543814]

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Article Details

Year: 2020
Published on: 25 April, 2020
Page: [144 - 149]
Pages: 6
DOI: 10.2174/1874467212666191119094636
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