MiR-514a-3p Inhibits Cell Proliferation and Epithelial-mesenchymal Transition by Targeting EGFR in Clear Cell Renal Cell Carcinoma

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2018 Jan 10

PMID 29312487

Citations 11

Authors

Xinwen Ke

Xing Zeng

Xian Wei

Yuanqing Shen

Jiahua Gan

Huake Tang

Zhiquan Hu

Affiliations

Soon will be listed here.

Abstract

Purpose: Dysregulation of miR-514a-3p has been reported in multiple human malignancies. However, its biological function and molecular mechanisms in renal cell cancer (RCC) remain unclear. The aims of this study were to explore the role of miR-514a-3p and its potential mechanism in human RCC.

Methods: The expression level of miR-514a-3p was quantified by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 20 cases of paired ccRCC and adjacent normal tissues and RCC cell lines. The role of miR-514a-3p in RCC cells was further evaluated by functional analyses. Western blot was applied to probe into the biological mechanism of miR-514a-3p in RCC cells.

Results: The qRT-PCR results confirmed that miR-514a-3p was dramatically down-regulated in ccRCC specimens. Restoration of miR-514a-3p expression might distinctively suppress cell proliferation, viability, migration and invasion in comparison with negative control in RCC cells and negatively regulate the proteins related to epithelial-mesenchymal transition (EMT), such as E-Cadherin, N-Cadherin and Vimentin. Results of luciferase reporter assay and Western blot analysis identified that miR-514a-3p might inversely regulate the expression of epidermal growth factor receptor (EGFR) directly by binding to its 3'-untranslated region (3'-UTR) at the translational level. Further studies showed that the phenotypic changes of RCC cells caused by miR-514a-3p occurred through EGFR/MAPK/ERK pathway rather than PI3K/AKT signaling. Moreover, the inhibitory effect of miR-514a-3p was also confirmed in vivo study.

Conclusions: MiR-514a-3p is a novel tumor suppressor in ccRCC and potentially functions through EGFR/MAPK/ERK pathway.

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References

Li M, Wang Y, Song Y, Bu R, Yin B, Fei X . MicroRNAs in renal cell carcinoma: a systematic review of clinical implications (Review). Oncol Rep. 2015; 33(4):1571-8. PMC: 4358077. DOI: 10.3892/or.2015.3799. View

Kurozumi A, Goto Y, Okato A, Ichikawa T, Seki N . Aberrantly expressed microRNAs in bladder cancer and renal cell carcinoma. J Hum Genet. 2016; 62(1):49-56. DOI: 10.1038/jhg.2016.84. View

Li S, Zhang H, Ning T, Wang X, Liu R, Yang H . MiR-520b/e Regulates Proliferation and Migration by Simultaneously Targeting EGFR in Gastric Cancer. Cell Physiol Biochem. 2016; 40(6):1303-1315. DOI: 10.1159/000453183. View

Lewis B, Burge C, Bartel D . Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005; 120(1):15-20. DOI: 10.1016/j.cell.2004.12.035. View

Shelton J, Steelman L, Abrams S, White E, Akula S, Franklin R . Conditional EGFR promotes cell cycle progression and prevention of apoptosis in the absence of autocrine cytokines. Cell Cycle. 2005; 4(6):822-30. DOI: 10.4161/cc.4.6.1724. View

Nam E, Kim S, Lee T, Kim H, Lee J, Kim S . Primary and recurrent ovarian high-grade serous carcinomas display similar microRNA expression patterns relative to those of normal ovarian tissue. Oncotarget. 2016; 7(43):70524-70534. PMC: 5342571. DOI: 10.18632/oncotarget.12045. View

Meng F, Wang F, Wang L, Wong S, Cho W, Chan L . MiR-30a-5p Overexpression May Overcome EGFR-Inhibitor Resistance through Regulating PI3K/AKT Signaling Pathway in Non-small Cell Lung Cancer Cell Lines. Front Genet. 2016; 7:197. PMC: 5108768. DOI: 10.3389/fgene.2016.00197. View

Weng L, Wu X, Gao H, Mu B, Li X, Wang J . MicroRNA profiling of clear cell renal cell carcinoma by whole-genome small RNA deep sequencing of paired frozen and formalin-fixed, paraffin-embedded tissue specimens. J Pathol. 2010; 222(1):41-51. DOI: 10.1002/path.2736. View

Kowalik C, Palmer D, Sullivan T, Teebagy P, Dugan J, Libertino J . Profiling microRNA from nephrectomy and biopsy specimens: predictors of progression and survival in clear cell renal cell carcinoma. BJU Int. 2017; 120(3):428-440. DOI: 10.1111/bju.13886. View

10.

Holbro T, Civenni G, Hynes N . The ErbB receptors and their role in cancer progression. Exp Cell Res. 2003; 284(1):99-110. DOI: 10.1016/s0014-4827(02)00099-x. View

11.

Hsieh J, Purdue M, Signoretti S, Swanton C, Albiges L, Schmidinger M . Renal cell carcinoma. Nat Rev Dis Primers. 2017; 3:17009. PMC: 5936048. DOI: 10.1038/nrdp.2017.9. View

12.

Gowrishankar B, Ibragimova I, Zhou Y, Slifker M, Devarajan K, Al-Saleem T . MicroRNA expression signatures of stage, grade, and progression in clear cell RCC. Cancer Biol Ther. 2013; 15(3):329-41. PMC: 3974834. DOI: 10.4161/cbt.27314. View

13.

Stewart G, OMahony F, Powles T, Riddick A, Harrison D, Faratian D . What can molecular pathology contribute to the management of renal cell carcinoma?. Nat Rev Urol. 2011; 8(5):255-65. DOI: 10.1038/nrurol.2011.43. View

14.

Liu L, Liu S, Duan Q, Chen L, Wu T, Qian H . MicroRNA-142-5p promotes cell growth and migration in renal cell carcinoma by targeting BTG3. Am J Transl Res. 2017; 9(5):2394-2402. PMC: 5446521. View

15.

Jung M, Mollenkopf H, Grimm C, Wagner I, Albrecht M, Waller T . MicroRNA profiling of clear cell renal cell cancer identifies a robust signature to define renal malignancy. J Cell Mol Med. 2009; 13(9B):3918-28. PMC: 4516539. DOI: 10.1111/j.1582-4934.2009.00705.x. View

16.

Ge Y, Wu R, Xin H, Zhu M, Lu T, Liu H . A tumor-specific microRNA signature predicts survival in clear cell renal cell carcinoma. J Cancer Res Clin Oncol. 2015; 141(7):1291-9. DOI: 10.1007/s00432-015-1927-0. View

17.

Stumm G, Eberwein S, STEIN H, Pomer S, Schlegel J, Waldherr R . Concomitant overexpression of the EGFR and erbB-2 genes in renal cell carcinoma (RCC) is correlated with dedifferentiation and metastasis. Int J Cancer. 1996; 69(1):17-22. DOI: 10.1002/(SICI)1097-0215(19960220)69:1<17::AID-IJC4>3.0.CO;2-Z. View

18.

Al-Ali B, Ress A, Gerger A, Pichler M . MicroRNAs in renal cell carcinoma: implications for pathogenesis, diagnosis, prognosis and therapy. Anticancer Res. 2012; 32(9):3727-32. View

19.

Slaby O, Jancovicova J, Lakomy R, Svoboda M, Poprach A, Fabian P . Expression of miRNA-106b in conventional renal cell carcinoma is a potential marker for prediction of early metastasis after nephrectomy. J Exp Clin Cancer Res. 2010; 29:90. PMC: 2907341. DOI: 10.1186/1756-9966-29-90. View

20.

Catto J, Alcaraz A, Bjartell A, de Vere White R, Evans C, Fussel S . MicroRNA in prostate, bladder, and kidney cancer: a systematic review. Eur Urol. 2011; 59(5):671-81. DOI: 10.1016/j.eururo.2011.01.044. View