title: miRNA-30a functions as a tumor suppressor by downregulating cyclin E2 expression in castration-resistant prostate cancer.
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.
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Zhang
authors.affiliation: Surgical Research Center, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Chun-Hui
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Lu
authors.affiliation: Surgical Research Center, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Ye-Qing
authors.initials: YQ
authors.lastname: Huang
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Yi-Duo
authors.initials: YD
authors.lastname: Wang
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Xing
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Shu-Qiu
authors.initials: SQ
authors.lastname: Chen
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001665:Binding Sites; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D016213:Cyclins / Q000235:genetics*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D047368:Tumor Burden
chemical_list: D020413:3' Untranslated Regions; C503688:CCNE2 protein, human; D016213:Cyclins; C546086:MIRN30b microRNA, human; D035683:MicroRNAs