microRNA-503 suppresses the migration, proliferation and colony formation of prostate cancer cells by targeting tumor protein D52 like 2

Chi,Yuhua; Ding,Feng; Zhang,Wenjie; Du,Lifa

doi:10.3892/etm.2017.5401

microRNA-503 suppresses the migration, proliferation and colony formation of prostate cancer cells by targeting tumor protein D52 like 2

Authors:
- Yuhua Chi
- Feng Ding
- Wenjie Zhang
- Lifa Du
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Affiliations: Department of Oncology, People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China, Department of Anesthesia Surgery, People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China
Published online on: October 30, 2017 https://doi.org/10.3892/etm.2017.5401
Pages: 473-478

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Abstract

The present study investigated the expression of microRNA‑503 (miR‑503) and its effect and mechanism of action on prostate cancer. Tumor tissues and tumor‑adjacent tissues were collected from 20 patients with prostate cancer. TargetScan was used to predict the miRNA molecule that interacts with tumor protein D52 like 2 (TPD52L2). DU145 cells were transfected with a negative control, miR‑503 mimic or miR‑503 inhibitor. DU145 cells that had not undergone transfection were used as a control. Levels of miR‑503 and TPD52L2 mRNA were determined using reverse transcription-quantitative polymerase chain reaction and the expression of TPD52L2 protein was measured using western blot analysis. The migration ability of DU145 cells was evaluated using a Transwell assay and cell proliferation was examined using an MTT assay. A flat plate colony formation test was conducted to examine the colony formation rate of DU145 cells. The current study demonstrated that TPD52L2 expression is increased while miR‑503 expression is decreased in prostate cancer tissues. Overexpression of miR‑503 inhibited the transcription and translation of TPD52L2 in DU145 cells and reduced cell migration, proliferation and colony formation. By contrast, inhibition of miR‑503 expression increased the expression of TPD52L2 in DU145 cells and increased cell migration, proliferation and colony formation. The present study demonstrated that miR‑503 is an oncogene that regulates the migration, proliferation and colony formation of prostate cancer cells by targeting the TPD52L2 gene. Thus, miR‑503 has the potential to become a target for the molecular treatment and prognosis of prostate cancer in the future.

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1	Grönberg H: Prostate cancer epidemiology. Lancet. 361:859–864. 2003. View Article : Google Scholar : PubMed/NCBI
2	Wong YC and Wang YZ: Growth factors and epithelial-stromal interactions in prostate cancer development. Int Rev Cytol. 199:65–116. 2000. View Article : Google Scholar : PubMed/NCBI
3	Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, Arora VK, Kaushik P, Cerami E, Reva B, et al: Integrative genomic profiling of human prostate cancer. Cancer Cell. 18:11–22. 2010. View Article : Google Scholar : PubMed/NCBI
4	Devaney JM, Wang S, Funda S, Long J, Taghipour DJ, Tbaishat R, Furbert-Harris P, Ittmann M and Kwabi-Addo B: Identification of novel DNA-methylated genes that correlate with human prostate cancer and high-grade prostatic intraepithelial neoplasia. Prostate Cancer Prostatic Dis. 16:292–300. 2013. View Article : Google Scholar : PubMed/NCBI
5	Marcelli M, Ittmann M, Mariani S, Sutherland R, Nigam R, Murthy L, Zhao Y, DiConcini D, Puxeddu E, Esen A, et al: Androgen receptor mutations in prostate cancer. Cancer Res. 60:944–949. 2000.PubMed/NCBI
6	Boutros R, Fanayan S, Shehata M and Byrne JA: The tumor protein D52 family: Many pieces, many puzzles. Biochem Biophys Res Commun. 325:1115–1121. 2004. View Article : Google Scholar : PubMed/NCBI
7	Thomas DD, Martin CL, Weng N, Byrne JA and Groblewski GE: Tumor protein D52 expression and Ca2+-dependent phosphorylation modulates lysosomal membrane protein trafficking to the plasma membrane. Am J Physiol Cell Physiol. 298:C725–C739. 2010. View Article : Google Scholar : PubMed/NCBI
8	Balleine RL, Fejzo MS, Sathasivam P, Basset P, Clarke CL and Byrne JA: The hD52 (TPD52) gene is a candidate target gene for events resulting in increased 8q21 copy number in human breast carcinoma. Genes Chromosomes Cancer. 29:48–57. 2000. View Article : Google Scholar : PubMed/NCBI
9	Wang Y, Chen CL, Pan QZ, Wu YY, Zhao JJ, Jiang SS, Chao J, Zhang XF, Zhang HX, Zhou ZQ, et al: Decreased TPD52 expression is associated with poor prognosis in primary hepatocellular carcinoma. Oncotarget. 7:6323–6334. 2016. View Article : Google Scholar : PubMed/NCBI
10	Wang Z, Sun J, Zhao Y, Guo W, Lv K and Zhang Q: Lentivirus-mediated knockdown of tumor protein D52-like 2 inhibits glioma cell proliferation. Cell Mol Biol (Noisy-le-grand). 60:39–44. 2014.PubMed/NCBI
11	Pan ZY, Yang Y, Pan H, Zhang J, Liu H, Yang Y, Huang G, Yin L, Huang J and Zhou WP: Lentivirus-mediated TPD52L2 depletion inhibits the proliferation of liver cancer cells in vitro. Int J Clin Exp Med. 8:2334–2341. 2015.PubMed/NCBI
12	Almeida MI, Reis RM and Calin GA: MicroRNA history: Discovery, recent applications, and next frontiers. Mutat Res. 717:1–8. 2011. View Article : Google Scholar : PubMed/NCBI
13	Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL and Visakorpi T: MicroRNA expression profiling in prostate cancer. Cancer Res. 67:6130–6135. 2007. View Article : Google Scholar : PubMed/NCBI
14	Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D'Urso L, Pagliuca A, Biffoni M, Labbaye C, et al: The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 14:1271–1277. 2008. View Article : Google Scholar : PubMed/NCBI
15	Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT and Dang CV: c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature. 458:762–765. 2009. View Article : Google Scholar : PubMed/NCBI
16	Zhao JJ, Yang J, Lin J, Yao N, Zhu Y, Zheng J, Xu J, Cheng JQ, Lin JY and Ma X: Identification of miRNAs associated with tumorigenesis of retinoblastoma by miRNA microarray analysis. Childs Nerv Syst. 25:13–20. 2009. View Article : Google Scholar : PubMed/NCBI
17	Watahiki A and Wang Y, Morris J, Dennis K, O'Dwyer HM, Gleave M, Gout PW and Wang Y: MicroRNAs associated with metastatic prostate cancer. PLoS One. 6:e249502011. View Article : Google Scholar : PubMed/NCBI
18	Qiu T, Zhou L, Wang T, Xu J, Wang J, Chen W, Zhou X, Huang Z, Zhu W, Shu Y and Liu P: miR-503 regulates the resistance of non-small cell lung cancer cells to cisplatin by targeting Bcl-2. Int J Mol Med. 32:593–598. 2013. View Article : Google Scholar : PubMed/NCBI
19	Epstein JI, Allsbrook WC Jr, Amin MB and Egevad LL: ISUP Grading Committee: The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol. 29:1228–1242. 2005. View Article : Google Scholar : PubMed/NCBI
20	Chomczynski P and Sacchi N.: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 162:156–159. 1987. View Article : Google Scholar : PubMed/NCBI
21	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
22	Li W, Ma H and Sun J: microRNA-34a/c function as tumor suppressors in Hep-2 laryngeal carcinoma cells and may reduce GALNT7 expression. Mol Med Rep. 9:1293–1298. 2014. View Article : Google Scholar : PubMed/NCBI
23	Esquela-Kerscher A and Slack FJ: Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
24	Zhou B, Ma R, Si W, Li S, Xu Y, Tu X and Wang Q: MicroRNA-503 targets FGF2 and VEGFA and inhibits tumor angiogenesis and growth. Cancer Lett. 333:159–169. 2013. View Article : Google Scholar : PubMed/NCBI
25	Ummanni R, Teller S, Junker H, Zimmermann U, Venz S, Scharf C, Giebel J and Walther R: Altered expression of tumor protein D52 regulates apoptosis and migration of prostate cancer cells. FEBS J. 275:5703–5713. 2008. View Article : Google Scholar : PubMed/NCBI
26	Zhou J, Tao Y, Peng C, Gu P and Wang W: miR-503 regulates metastatic function through Rho guanine nucleotide exchanger factor 19 in hepatocellular carcinoma. J Surg Res. 188:129–136. 2014. View Article : Google Scholar : PubMed/NCBI
27	Yang Y, Liu L, Zhang Y, Guan H, Wu J, Zhu X, Yuan J and Li M: MiR-503 targets PI3K p85 and IKK-β and suppresses progression of non-small cell lung cancer. Int J Cancer. 135:1531–1542. 2014. View Article : Google Scholar : PubMed/NCBI
28	Wang T, Ge G, Ding Y, Zhou X, Huang Z, Zhu W, Shu Y and Liu P: MiR-503 regulates cisplatin resistance of human gastric cancer cell lines by targeting IGF1R and BCL2. Chin Med J (Engl). 127:2357–2362. 2014.PubMed/NCBI
29	Li L, Sarver AL, Khatri R, Hajeri PB, Kamenev I, French AJ, Thibodeau SN, Steer CJ and Subramanian S: Sequential expression of miR-182 and miR-503 cooperatively targets FBXW7, contributing to the malignant transformation of colon adenoma to adenocarcinoma. J Pathol. 234:488–501. 2014. View Article : Google Scholar : PubMed/NCBI
30	Wu Y, Guo L, Liu J, Liu R, Liu M and Chen J: The reversing and molecular mechanisms of miR-503 on the drug-resistance to cisplatin in A549/DDP cells. Zhongguo Fei Ai Za Zhi. 17:1–7. 2014.(In Chinese). PubMed/NCBI
31	Polioudakis D, Abell NS and Iyer VR: miR-503 represses human cell proliferation and directly targets the oncogene DDHD2 by non-canonical target pairing. BMC Genomics. 16:402015. View Article : Google Scholar : PubMed/NCBI