Tumor suppressor microRNA‑136‑5p regulates the cellular function of renal cell carcinoma

Chen,Peijie; Zhao,Liwen; Pan,Xiang; Jin,Lu; Lin,Canbin; Xu,Weijie; Xu,Jinling; Guan,Xin; Wu,Xueling; Wang,Yong; Yang,Shangqi; Wang,Tao; Lai,Yongqing

doi:10.3892/ol.2018.8081

Tumor suppressor microRNA‑136‑5p regulates the cellular function of renal cell carcinoma

Authors:
- Peijie Chen
- Liwen Zhao
- Xiang Pan
- Lu Jin
- Canbin Lin
- Weijie Xu
- Jinling Xu
- Xin Guan
- Xueling Wu
- Yong Wang
- Shangqi Yang
- Tao Wang
- Yongqing Lai
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Affiliations: Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China, Department of Urology, Longgang District Central Hospital of Shenzhen, Shenzhen, Guangdong 518116, P.R. China, Department of Reproduction, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China, Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
Published online on: February 16, 2018 https://doi.org/10.3892/ol.2018.8081
Pages: 5995-6002

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Abstract

MicroRNAs (miRs) are involved in diverse physiological and developmental processes at the post-transcriptional level in cells. Previous studies have demonstrated that miR‑136‑5p is involved in certain types of cancer. However, the function of miR‑136‑5p in renal cell carcinoma (RCC) remains to be fully elucidated. In present study, miR‑136‑5p expression levels were determined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and MTT assays, CCK‑8 assays, Transwell assays, wound healing assays and flow cytometry were performed to investigate the function of miR‑136‑5p in RCC. RT‑qPCR revealed that the expression of miR‑136 was significantly lower in RCC tissues and cells compared with adjacent non‑tumor tissues and cells in vitro. miR‑136‑5pwas also demonstrated to be associated with RCC cell proliferation, viability, migration, invasion and apoptosis. miR‑136‑5p may therefore function as a tumor suppressor in RCC. Further studies are required to elucidate the molecular mechanisms and signaling pathways underlying these functions of miR‑136‑5p, to investigate the potential function of miR‑136‑5p as a biomarker for the early detection and prognosis of RCC, and its potential as a therapeutic target for the treatment of RCC.

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1	Wang Z, Qin C, Zhang J, Han Z, Tao J, Cao Q, Zhou W, Xu Z, Zhao C, Tan R and Gu M: MiR-122 promotes renal cancer cell proliferation by targeting Sprouty 2. Tumour Biol. 39:10104283176911842017.PubMed/NCBI
2	Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L, Schmidinger M, Heng DY, Larkin J and Ficarra V: Renal cell carcinoma. Nat Rev Dis Primers. 3:170092017. View Article : Google Scholar : PubMed/NCBI
3	Bharthuar A, Pandey H and Sood S: Management of metastatic renal cell carcinoma-mini review. J Kidney Cancer VHL. 2:75–83. 2015. View Article : Google Scholar : PubMed/NCBI
4	Teixeira AL, Dias F, Gomes M, Fernandes M and Medeiros R: Circulating biomarkers in renal cell carcinoma: The link between microRNAs and extracellular vesicles, where are we now? J Kidney Cancer VHL. 1:84–98. 2014. View Article : Google Scholar : PubMed/NCBI
5	Ljungberg B, Bensalah K, Canfield S, Dabestani S, Hofmann F, Hora M, Kuczyk MA, Lam T, Marconi L, Merseburger AS, et al: EAU guidelines on renal cell carcinoma: 2014 update. Eur Urol. 67:913–924. 2015. View Article : Google Scholar : PubMed/NCBI
6	Aguiari G: MicroRNAs in clear cell renal cell carcinoma: Biological functions and applications. J Kidney Cancer VHL. 2:140–152. 2015. View Article : Google Scholar : PubMed/NCBI
7	Ling H, Girnita L, Buda O and Calin GA: Non-coding RNAs: The cancer genome dark matter that matters! Clin Chem Lab Med. 55:1–714. 2017. View Article : Google Scholar : PubMed/NCBI
8	Liang T, Hu XY, Li YH, Tian BQ, Li ZW and Fu Q: MicroRNA-21 regulates the proliferation, differentiation, and apoptosis of human renal cell carcinoma cells by the mTOR-STAT3 signaling pathway. Oncol Res. 24:371–380. 2016. View Article : Google Scholar : PubMed/NCBI
9	Xiao H, Xiao W, Cao J, Li H, Guan W, Guo X, Chen K, Zheng T, Ye Z, Wang J and Xu H: miR-206 functions as a novel cell cycle regulator and tumor suppressor in clear-cell renal cell carcinoma. Cancer Lett. 374:107–116. 2016. View Article : Google Scholar : PubMed/NCBI
10	Liu F, Chen N, Xiao R, Wang W and Pan Z: miR-144-3p serves as a tumor suppressor for renal cell carcinoma and inhibits its invasion and metastasis by targeting MAP3K8. Biochem Biophys Res Commun. 480:87–93. 2016. View Article : Google Scholar : PubMed/NCBI
11	Jeong JY, Kang H, Kim TH, Kim G, Heo JH, Kwon AY, Kim S, Jung SG and An HJ: MicroRNA-136 inhibits cancer stem cell activity and enhances the anti-tumor effect of paclitaxel against chemoresistant ovarian cancer cells by targeting Notch3. Cancer Lett. 386:168–178. 2017. View Article : Google Scholar : PubMed/NCBI
12	Yan M, Li X, Tong D, Han C, Zhao R, He Y and Jin X: miR-136 suppresses tumor invasion and metastasis by targeting RASAL2 in triple-negative breast cancer. Oncol Rep. 36:65–71. 2016. View Article : Google Scholar : PubMed/NCBI
13	Shen S, Yue H, Li Y, Qin J, Li K, Liu Y and Wang J: Upregulation of miR-136 in human non-small cell lung cancer cells promotes Erk1/2 activation by targeting PPP2R2A. Tumour Biol. 35:631–640. 2014. View Article : Google Scholar : PubMed/NCBI
14	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
15	Dweep H, Sticht C, Pandey P and Gretz N: miRWalk-database: Prediction of possible miRNA binding sites by ‘walking’ the genes of three genomes. J Biomed Inform. 44:839–847. 2011. View Article : Google Scholar : PubMed/NCBI
16	Enright AJ, John B, Gaul U, Tuschl T, Sander C and Marks DS: MicroRNA targets in Drosophila. Genome Biol. 5:R12003. View Article : Google Scholar : PubMed/NCBI
17	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
18	Kotlabova K, Doucha J and Hromadnikova I: Placental-specific microRNA in maternal circulation-identification of appropriate pregnancy-associated microRNAs with diagnostic potential. J Reprod Immunol. 89:185–191. 2011. View Article : Google Scholar : PubMed/NCBI
19	Tusong H, Maolakuerban N, Guan J, Rexiati M, Wang WG, Azhati B, Nuerrula Y and Wang YJ: Functional analysis of serum microRNAs miR-21 and miR-106a in renal cell carcinoma. Cancer Biomarker. 18:79–85. 2017. View Article : Google Scholar
20	Yang Y, Liu L, Cai J, Wu J, Guan H, Zhu X, Yuan J, Chen S and Li M: Targeting Smad2 and Smad3 by miR-136 suppresses metastasis-associated traits of lung adenocarcinoma cells. Oncol Res. 21:345–352. 2013. View Article : Google Scholar : PubMed/NCBI
21	Mosakhani N, Pazzaglia L, Benassi MS, Borze I, Quattrini I, Picci P and Knuutila S: MicroRNA expression profiles in metastatic and non-metastatic giant cell tumor of bone. Histol Histopathol. 28:671–678. 2013.PubMed/NCBI
22	Yang Y, Wu J, Guan H, Cai J, Fang L, Li J and Li M: MiR-136 promotes apoptosis of glioma cells by targeting AEG-1 and Bcl-2. FEBS Lett. 586:3608–3612. 2012. View Article : Google Scholar : PubMed/NCBI
23	Jeansonne D, Pacifici M, Lassak A, Reiss K, Russo G, Zabaleta J and Peruzzi F: Differential effects of MicroRNAs on glioblastoma growth and migration. Genes (Basel). 4:46–64. 2013. View Article : Google Scholar : PubMed/NCBI
24	Zhao H, Liu S, Wang G, Wu X, Ding Y, Guo G, Jiang J and Cui S: Expression of miR-136 is associated with the primary cisplatin resistance of human epithelial ovarian cancer. Oncol Rep. 33:591–598. 2015. View Article : Google Scholar : PubMed/NCBI
25	Gao H, Song X, Kang T, Yan B, Feng L, Gao L, Ai L, Liu X, Yu J and Li H: Long noncoding RNA CRNDE functions as a competing endogenous RNA to promote metastasis and oxaliplatin resistance by sponging miR-136 in colorectal cancer. Onco Targets Ther. 10:205–216. 2017. View Article : Google Scholar : PubMed/NCBI
26	Hao JF, Ren KM, Bai JX, Wang SN, Shao B, Cao N and Li X: Identification of potential biomarkers for clear cell renal cell carcinoma based on microRNA-mRNA pathway relationships. J Cancer Res Ther. 10 Suppl:C167–C177. 2014. View Article : Google Scholar : PubMed/NCBI
27	Wu H, Liu Q, Cai T, Chen YD, Liao F and Wang ZF: MiR-136 modulates glioma cell sensitivity to temozolomide by targeting astrocyte elevated gene-1. Diagn Pathol. 9:1732014. View Article : Google Scholar : PubMed/NCBI
28	Chen W, Yang Y, Chen B, Lu P, Zhan L, Yu Q, Cao K and Li Q: MiR-136 targets E2F1 to reverse cisplatin chemosensitivity in glioma cells. J Neurooncol. 120:43–53. 2014. View Article : Google Scholar : PubMed/NCBI
29	Zhao J, Wang W, Huang Y, Wu J, Chen M, Cui P, Zhang W and Zhang Y: HBx elevates oncoprotein AEG-1 expression to promote cell migration by downregulating miR-375 and miR-136 in malignant hepatocytes. DNA Cell Biol. 33:715–722. 2014. View Article : Google Scholar : PubMed/NCBI
30	Ji L, Zhang L, Li Y, Guo L, Cao N, Bai Z, Song Y, Xu Z, Zhang J, Liu C and Ma X: MiR-136 contributes to pre-eclampsia through its effects on apoptosis and angiogenesis of mesenchymal stem cells. Placenta. 50:102–109. 2017. View Article : Google Scholar : PubMed/NCBI
31	Zhang D, Wang J, Wang Z, Zhang T, Shi P, Wang X, Zhao F, Liu X, Lin X and Pang X: miR-136 modulates TGF-beta1-induced proliferation arrest by targeting PPP2R2A in keratinocytes. Biomed Res Int. 2015:4535182015.PubMed/NCBI
32	Zhang CF, Kang K, Li XM and Xie BD: MicroRNA-136 promotes vascular muscle cell proliferation through the ERK1/2 pathway by targeting PPP2R2A in atherosclerosis. Curr Vasc Pharmacol. 13:405–412. 2015. View Article : Google Scholar : PubMed/NCBI
33	Zhang B, Pan X, Cobb GP and Anderson TA: microRNAs as oncogenes and tumor suppressors. Dev Biol. 302:1–12. 2007. View Article : Google Scholar : PubMed/NCBI