miRNA-30a functions as a tumor suppressor by downregulating cyclin E2 expression in castration-resistant prostate cancer

Zhang,Lei; Zhang,Xiao‑Wen; Liu,Chun‑Hui; Lu,Kai; Huang,Ye‑Qing; Wang,Yi‑Duo; Xing,Li; Zhang,Li‑Jie; Liu,Ning; Jiang,Hua; Sun,Chao; Yang,Yu; Chen,Shu‑Qiu; Chen,Ming; Xu,Bin

doi:10.3892/mmr.2016.5469

miRNA-30a functions as a tumor suppressor by downregulating cyclin E2 expression in castration-resistant prostate cancer

Authors:
- Lei Zhang
- Xiao‑Wen Zhang
- Chun‑Hui Liu
- Kai Lu
- Ye‑Qing Huang
- Yi‑Duo Wang
- Li Xing
- Li‑Jie Zhang
- Ning Liu
- Hua Jiang
- Chao Sun
- Yu Yang
- Shu‑Qiu Chen
- Ming Chen
- Bin Xu
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Affiliations: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China, Surgical Research Center, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China
Published online on: July 6, 2016 https://doi.org/10.3892/mmr.2016.5469
Pages: 2077-2084

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Abstract

MicroRNAs (miRNAs) act as tumor promoters or tumor suppressors in different human malignancies. In the current study, using an Agilent miRNA microarray, miR‑30a was found to be a significantly downregulated miRNA in castration‑resistant prostate cancer (CRPC) tissues, compared with androgen‑dependent prostate cancer tissues. Aberrant expression of cyclin E2 (CCNE2) has been reported in a variety of types of cancer including prostate cancer, and correlates with clinical outcome. The purpose of the current study was to determine the functions of miR‑30a in CRPC cell lines and identify whether CCNE2 was regulated by miR‑30a. To analyze the associations between miR‑30a and CCNE2 expression levels, pathological specimens were collected, and reverse transcription‑quantitative polymerase chain reaction and immunohistochemical staining were conducted. The effect of miR‑30a overexpression on CRPC cell lines and the predicted target gene, CCNE2, were evaluated by MTT assay, flow cytometry, tumor formation, luciferase reporter assay and western blotting. miR‑30a overexpression resulted in a significant suppression of cell growth in vitro, and reduced tumorigenicity in vivo. miR‑30a repressed the expression of CCNE2 through binding to its 3'‑untranslated region. CCNE2 was observed to be overexpressed in patients with CRCP and had an approximately inverse correlation with the level of miR‑30a. The results suggest that miR‑30a may function as a novel tumor suppressor in CRPC. Its anti‑oncogenic activity may occur by the reduced expression of a distinct cell cycle protein, CCNE2.

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