microRNA‑572 functions as an oncogene and a potential biomarker for renal cell carcinoma prognosis

Pan,Xiang; Li,Zuwei; Zhao,Liwen; Quan,Jing; Zhou,Liang; Xu,Jinling; Xu,Weiji; Guan,Xin; Li,Hang; Yang,Shangqi; Gui,Yaoting; Lai,Yongqing

doi:10.3892/or.2018.6649

microRNA‑572 functions as an oncogene and a potential biomarker for renal cell carcinoma prognosis

Authors:
- Xiang Pan
- Zuwei Li
- Liwen Zhao
- Jing Quan
- Liang Zhou
- Jinling Xu
- Weiji Xu
- Xin Guan
- Hang Li
- Shangqi Yang
- Yaoting Gui
- Yongqing Lai
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Affiliations: Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China, The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China
Published online on: August 17, 2018 https://doi.org/10.3892/or.2018.6649
Pages: 3092-3101

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Abstract

Renal cell carcinoma (RCC) is the third most common urological malignancy in the USA and represents 2‑3% of all adult malignancies. Furthermore, the incidence of RCC has been progressively increasing over recent years. Although the morbidity of treatment has decreased with the use of multidisciplinary synthetic therapy, the prognosis of terminal cancer remains poor, with a 5‑year survival rate of 5‑10%. MicroRNAs (miRs) have been correlated with the regulation of 30‑60% of the proteincoding genes and act as oncogenes or anti‑oncogenes in RCC. Considering this research, miRNAs are likely to be the biomarkers for tumor diagnosis, prognosis and the targets for RCC management. In the present study, 42 formalin‑fixed paraffin‑embedded RCC samples were used. The expression of miR‑572 and the role of miR‑572 in RCC cell proliferation, migration and apoptosis was determined by performing reverse transcription‑quantitative polymerase chain reaction analysis, wound scratch assays, cell proliferation assays, Transwell assays and flow cytometry assays, respectively. Further experiments were conducted to clarify the correlation between miR‑572 expression and clinicopathological variables or overall survival. Furthermore, the expression levels of miR‑572 were evaluated for the prognosis value of patients with RCC. Upregulation of miR‑572 was observed in RCC tissues and RCC cell lines. miR‑572 promoted 786‑O and ACHN cell proliferation and mobility and inhibited early apoptosis. In Cox proportional hazard regression analyses, results of the univariate and multivariate analysis indicated that the patients with low miR‑572 expression had a significantly longer overall survival compared with the patients with high miR‑572 expression (univariate analysis, P=0.037; multivariate analysis, P=0.034). Results of the Kaplan‑Meier survival curves revealed that the patients with downregulated miR‑572 have a significantly longer overall survival compared with the patients with highly expressed miR‑572 (P=0.019). To conclude, the results of the present study suggest that tumor oncogene miR‑572 is a potential biomarker for the diagnosis, treatment and prognosis for RCC.

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1	Petrozza V, Pastore AL, Palleschi G, Tito C, Porta N, Ricci S, Marigliano C, Costantini M, Simone G, Di Carlo A, et al: Secreted miR-210-3p as non-invasive biomarker in clear cell renal cell carcinoma. Oncotarget. 8:69551–69558. 2017. View Article : Google Scholar : PubMed/NCBI
2	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
3	King SC, Pollack LA, Li J, King JB and Master VA: Continued increase in incidence of renal cell carcinoma, especially in young patients and high grade disease: United States 2001 to 2010. J Urol. 191:1665–1670. 2014. View Article : Google Scholar : PubMed/NCBI
4	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
5	Rini BI, Campbell SC and Escudier B: Renal cell carcinoma. Lancet. 373:1119–1132. 2009. View Article : Google Scholar : PubMed/NCBI
6	Patel C, Ahmed A and Ellsworth P: Renal cell carcinoma: A reappraisal. Urol Nurs. 32:182–190; quiz 191. 2012.PubMed/NCBI
7	Hadoux J, Vignot S and De La Motte Rouge T: Renal cell carcinoma: Focus on safety and efficacy of temsirolimus. Clin Med Insights Oncol. 4:143–154. 2010. View Article : Google Scholar : PubMed/NCBI
8	Homami A and Ghazi F: MicroRNAs as biomarkers associated with bladder cancer. Med J Islamic Repub Iran. 30:4752016.
9	Enokida H, Yoshino H, Matsushita R and Nakagawa M: The role of microRNAs in bladder cancer. Investig Clin Urol. 1 Suppl 57:S60–S76. 2016. View Article : Google Scholar
10	Filipowicz W, Bhattacharyya SN and Sonenberg N: Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight? Nat Rev Genet. 9:102–114. 2008. View Article : Google Scholar : PubMed/NCBI
11	Hobert O: Gene regulation by transcription factors and microRNAs. Science. 319:1785–1786. 2008. View Article : Google Scholar : PubMed/NCBI
12	Ding D, Zhang Y, Wen L, Fu J, Bai X, Fan Y, Lin Y, Dai H, Li Q, Zhang Y, et al: MiR-367 regulates cell proliferation and metastasis by targeting metastasis-associated protein 3 (MTA3) in clear-cell renal cell carcinoma. Oncotarget. 8:63084–63095. 2017.PubMed/NCBI
13	Cai W, Jiang H, Yu Y, Xu Y, Zuo W, Wang S and Su Z: miR−367 regulation of DOC-2/DAB2 interactive protein promotes proliferation, migration and invasion of osteosarcoma cells. Biomed Pharmacother. 95:120–128. 2017. View Article : Google Scholar : PubMed/NCBI
14	Zhu DX, Zhu W, Fang C, Fan L, Zou ZJ, Wang YH, Liu P, Hong M, Miao KR, Liu P, et al: miR-181a/b significantly enhances drug sensitivity in chronic lymphocytic leukemia cells via targeting multiple anti-apoptosis genes. Carcinogenesis. 33:1294–1301. 2012. View Article : Google Scholar : PubMed/NCBI
15	Yan L, Cai K, Liang J, Liu H, Liu Y and Gui J: Interaction between miR-572 and PPP2R2C, and their effects on the proliferation, migration, and invasion of nasopharyngeal carcinoma (NPC) cells. Biochem Cell Biol. 95:578–584. 2017. View Article : Google Scholar : PubMed/NCBI
16	Wu AH, Huang YL, Zhang LZ, Tian G, Liao QZ and Chen SL: MiR-572 prompted cell proliferation of human ovarian cancer cells by suppressing PPP2R2C expression. Biomed Pharmacother. 77:92–97. 2016. View Article : Google Scholar : PubMed/NCBI
17	Sand M, Skrygan M, Sand D, Georgas D, Hahn SA, Gambichler T, Altmeyer P and Bechara FG: Expression of microRNAs in basal cell carcinoma. Br J Dermatol. 167:847–855. 2012. View Article : Google Scholar : PubMed/NCBI
18	Wang L, Tian H, Yuan J, Wu H, Wu J and Zhu X: CONSORT: Sam68 is directly regulated by MiR-204 and promotes the self-renewal potential of breast cancer cells by activating the wnt/beta-catenin signaling pathway. Medicine. 94:e22282015. View Article : Google Scholar : PubMed/NCBI
19	Edge SB and Compton CC: The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
21	Gupta K, Miller JD, Li JZ, Russell MW and Charbonneau C: Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): A literature review. Cancer Treat Rev. 34:193–205. 2008. View Article : Google Scholar : PubMed/NCBI
22	Kong YW, Ferland-McCollough D, Jackson TJ and Bushell M: microRNAs in cancer management. Lancet Oncol. 13:e249–258. 2012. View Article : Google Scholar : PubMed/NCBI
23	Hatziapostolou M, Polytarchou C and Iliopoulos D: miRNAs link metabolic reprogramming to oncogenesis. Trends Endocrinol Metab. 24:361–373. 2013. View Article : Google Scholar : PubMed/NCBI
24	Sellitti DF and Doi SQ: MicroRNAs in renal cell carcinoma. Microrna. 4:26–35. 2015. View Article : Google Scholar : PubMed/NCBI
25	Dey N, Das F, Ghosh-Choudhury N, Mandal CC, Parekh DJ, Block K, Kasinath BS, Abboud HE and Choudhury GG: microRNA-21 governs TORC1 activation in renal cancer cell proliferation and invasion. PLoS One. 7:e373662012. View Article : Google Scholar : PubMed/NCBI
26	Liu W, Zabirnyk O, Wang H, Shiao YH, Nickerson ML, Khalil S, Anderson LM, Perantoni AO and Phang JM: miR-23b* targets proline oxidase, a novel tumor suppressor protein in renal cancer. Oncogene. 29:4914–4924. 2010. View Article : Google Scholar : PubMed/NCBI
27	Zhang X, Wang C, Li H, Niu X, Liu X, Pei D, Guo X, Xu X and Li Y: miR-338-3p inhibits the invasion of renal cell carcinoma by downregulation of ALK5. Oncotarget. 8:64106–64113. 2017.PubMed/NCBI
28	Chen C, Xue S, Zhang J, Chen W, Gong D, Zheng J, Ma J, Xue W, Chen Y, Zhai W, et al: DNA-methylation-mediated repression of miR-766-3p promotes cell proliferation via targeting SF2 expression in renal cell carcinoma. Int J Cancer. 141:1867–1878. 2017. View Article : Google Scholar : PubMed/NCBI
29	Mundalil Vasu M, Anitha A, Takahashi T, Thanseem I, Iwata K, Asakawa T and Suzuki K: Fluoxetine increases the expression of miR-572 and miR-663a in human neuroblastoma cell lines. PLoS One. 11:e01644252016. View Article : Google Scholar : PubMed/NCBI
30	Yu X, Liu S, Li J, Fan X, Chen Y, Bi X, Liu S and Deng X: MicroRNA-572 improves early post-operative cognitive dysfunction by down-regulating neural cell adhesion molecule 1. PLoS One. 10:e01185112015. View Article : Google Scholar : PubMed/NCBI
31	Zhang X, Liu J, Zang D, Wu S, Liu A, Zhu J, Wu G, Li J and Jiang L: Upregulation of miR-572 transcriptionally suppresses SOCS1 and p21 and contributes to human ovarian cancer progression. Oncotarget. 6:15180–15193. 2015.PubMed/NCBI