miR‑19a‑3p targets PMEPA1 and induces prostate cancer cell proliferation, migration and invasion

Feng,Sujuan; Zhu,Xuhui; Fan,Bohan; Xie,Dawei; Li,Tao; Zhang,Xiaodong

doi:10.3892/mmr.2016.5033

miR‑19a‑3p targets PMEPA1 and induces prostate cancer cell proliferation, migration and invasion

Authors:
- Sujuan Feng
- Xuhui Zhu
- Bohan Fan
- Dawei Xie
- Tao Li
- Xiaodong Zhang
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Affiliations: Institute of Uro‑Nephrology, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, P.R. China
Published online on: March 21, 2016 https://doi.org/10.3892/mmr.2016.5033
Pages: 4030-4038

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Abstract

Prostate cancer (PCa) is one of the most common malignant tumors in men. Studies have observed that microRNA (miR)‑19a‑3p expression levels are downregulated in several types of cancer, and yet the biological function and its underlying mechanisms in the pathogenesis of PCa remain unclear. In the current study, the expression pattern of miR‑19a‑3p in PCa tissues and cell lines was detected by reverse transcription‑quantitative polymerase chain reaction. The proliferative, migratory and invasive capacity of PCa cells were determined using EdU and Transwell assays following transfection with miR‑19a‑3p mimics. Additionally, the current study investigated the biological impact and regulation of prostate transmembrane protein androgen induced 1 (PMEPA1) in PCa cells by transfection with PMEPA1 small interfering (si)RNA. It was observed that miR‑19a‑3p was upregulated in PCa tissue samples and cell lines in vitro. Functional analysis also confirmed that miR‑19a‑3p overexpression promoted the proliferation, migration and invasion of PCa cells. Furthermore, PMEPA1 was identified as a direct target of miR‑19a‑3p, and siRNA knockdown of PMEPA1 resulted in increased proliferation, migration and invasion of PCa cells, which partially accounts for the effect of miR‑19a‑3p in tumor metastasis. In conclusion, the findings of the present study suggest that the upregulation of miR‑19a‑3p expression levels contributes to tumor progression and that one of its underlying mechanisms involves inhibition of PMEPA1 expression.

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1	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
2	Loblaw DA, Walker- Dilks C, Winquist E and Hotte SJ; Genitourinary Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence- Based Care: Systemic therapy in men with metastatic castration- resistant prostate cancer: A systematic review. Clin Oncol (R Coll Radiol). 25:406–430. 2013. View Article : Google Scholar
3	Hessels D and Schalken JA: Urinary biomarkers for prostate cancer: A review. Asian J Androl. 15:333–339. 2013. View Article : Google Scholar : PubMed/NCBI
4	Gong AY, Eischeid AN, Xiao J, Zhao J, Chen D, Wang ZY, Young CY and Chen XM: miR-17-5p targets the p300/CBP-associated factor and modulates androgen receptor transcriptional activity in cultured prostate cancer cells. BMC Cancer. 12:4922012. View Article : Google Scholar : PubMed/NCBI
5	Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y and Takahashi T: A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 65:9628–9632. 2005. View Article : Google Scholar : PubMed/NCBI
6	He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ and Hammond S: A microRNA polycistron as a potential human oncogene. Nature. 435:828–833. 2005. View Article : Google Scholar : PubMed/NCBI
7	Tagawa H and Seto M: A microRNA cluster as a target of genomic amplification in malignant lymphoma. Leukemia. 19:2013–2016. 2005. View Article : Google Scholar : PubMed/NCBI
8	Bosch DA: Stereotactic rostral mesencephalotomy in cancer pain and deafferentation pain. A series of 40 cases with follow-up results. J Neurosurg. 75:747–751. 1991. View Article : Google Scholar : PubMed/NCBI
9	Yang X, Du WW, Li H, Liu F, Khorshidi A, Rutnam ZJ and Yang BB: Both mature miR-17-5p and passenger strand miR-17-3p target TIMP3 and induce prostate tumor growth and invasion. Nucleic Acids Res. 41:9688–9704. 2013. View Article : Google Scholar : PubMed/NCBI
10	Yang J, Zhang Z, Chen C, Liu Y, Si Q, Chuang TH, Li N, Gomez-Cabrero A, Reisfeld RA, Xiang R and Luo Y: MicroRNA-19a-3p inhibits breast cancer progression and metastasis by inducing macrophage polarization through downregulated expression of Fra-1 proto-oncogene. Oncogene. 33:3014–3023. 2014. View Article : Google Scholar
11	Zheng G, Du L, Yang X, Zhang X, Wang L, Yang Y, Li J and Wang C: Serum microRNA panel as biomarkers for early diagnosis of colorectal adenocarcinoma. Br J Cancer. 111:1985–1992. 2014. View Article : Google Scholar : PubMed/NCBI
12	Zhi F, Shao N, Wang R, Deng D, Xue L, Wang Q, Zhang Y, Shi Y, Xia X, Wang S, et al: Identification of 9 serum microRNAs as potential noninvasive biomarkers of human astrocytoma. Neuro Oncol. 17:383–391. 2015.
13	Ohori M1, Wheeler TM and Scardino PT: The New American Joint Committee on Cancer and International Union Against Cancer TNM classification of prostate cancer. Clinicopathologic correlations. Cancer. 74:104–114. 1994. 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
15	Bali KK and Kuner R: Noncoding RNAs: Key molecules in understanding and treating pain. Trends Mol Med. 20:437–448. 2014. View Article : Google Scholar : PubMed/NCBI
16	Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, et al: Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 360:1320–1328. 2009. View Article : Google Scholar : PubMed/NCBI
17	Sylvestre Y, De Guire V, Querido E, Mukhopadhyay UK, Bourdeau V, Major F, Ferbeyre G and Chartrand P: An E2F/miR-20a autoregulatory feedback loop. J Biol Chem. 282:2135–2143. 2007. View Article : Google Scholar
18	Pesta M, Klecka J, Kulda V, Topolcan O, Hora M, Eret V, Ludvikova M, Babjuk M, Novak K, Stolz J and Holubec L: Importance of miR-20a expression in prostate cancer tissue. Anticancer Res. 30:3579–3583. 2010.PubMed/NCBI
19	Fuse M, Nohata N, Kojima S, Sakamoto S, Chiyomaru T, Kawakami K, Enokida H, Nakagawa M, Naya Y, Ichikawa T and Seki N: Restoration of miR-145 expression suppresses cell proliferation, migration and invasion in prostate cancer by targeting FSCN1. Int J Oncol. 38:1093–1101. 2011.PubMed/NCBI
20	Ribas J, Ni X, Haffner M, Wentzel EA, Salmasi AH, Chowdhury WH, Kudrolli TA, Yegnasubramanian S, Luo J, Rodriguez R, et al: miR-21: An androgen receptor-regulated microRNA that promotes hormone-dependent and hormone-independent prostate cancer growth. Cancer Res. 69:7165–7169. 2009. View Article : Google Scholar : PubMed/NCBI
21	Sun T, Wang Q, Balk S, Brown M, Lee GS and Kantoff P: The role of microRNA-221 and microRNA-222 in androgen-independent prostate cancer cell lines. Cancer Res. 69:3356–3363. 2009. View Article : Google Scholar : PubMed/NCBI
22	Leung CM, Chen TW, Li SC, Ho MR, Hu LY, Liu WS, Wu TT, Hsu PC, Chang HT and Tsai KW: MicroRNA expression profiles in human breast cancer cells after multifraction and single-dose radiation treatment. Oncol Rep. 31:2147–2156. 2014.PubMed/NCBI
23	Xu LL, Shi Y, Petrovics G, Sun C, Makarem M, Zhang W, Sesterhenn IA, McLeod DG, Sun L, Moul JW and Srivastava S: PMEPA1, an androgen-regulated NEDD4-binding protein, exhibits cell growth inhibitory function and decreased expression during prostate cancer progression. Cancer Res. 63:4299–4304. 2003.PubMed/NCBI
24	Ishkanian AS, Mallof CA, Ho J, Meng A, Albert M, Syed A, van der Kwast T, Milosevic M, Yoshimoto M, Squire JA, et al: High-resolution array CGH identifies novel regions of genomic alteration in intermediate-risk prostate cancer. Prostate. 69:1091–1100. 2009. View Article : Google Scholar : PubMed/NCBI
25	Rae FK, Hooper JD, Nicol DL and Clements JA: Characterization of a novel gene, STAG1/PMEPA1, upregulated in renal cell carcinoma and other solid tumors. Mol Carcinog. 2:44–53. 2001. View Article : Google Scholar
26	Tanner MM, Tirkkonen M, Kallioniemi A, Collins C, Stokke T, Karhu R, Kowbel D, Shadravan F, Hintz M, Kuo WL, et al: Increased copy number at 20q13 in breast cancer: Defining the critical region and exclusion of candidate genes. Cancer Res. 54:4257–4260. 1994.PubMed/NCBI
27	Reichling T, Goss KH, Carson DJ, Holdcraft RW, Ley-Ebert C, Witte D, Aronow BJ and Groden J: Transcriptional profiles of intestinal tumors in Apc(Min) mice are unique from those of embryonic intestine and identify novel gene targets dysregulated in human colorectal tumors. Cancer Res. 65:166–176. 2005.PubMed/NCBI
28	Liu R, Zhou Z, Huang J and Chen C: PMEPA1 promotes androgen receptor-negative prostate cell proliferation through suppressing the Smad3/4-c-Myc-p21 Cip1 signaling pathway. J Pathol. 223:683–694. 2011. View Article : Google Scholar : PubMed/NCBI
29	Hirokawa YS, Takagi A, Uchida K, Kozuka Y, Yoneda M, Watanabe M and Shiraishi T: High level expression of STAG1/PMEPA1 in an androgen-independent prostate cancer PC3 subclone. Cell Mol Biol Lett. 12:370–377. 2007. View Article : Google Scholar : PubMed/NCBI