title: Downregulation of miR-221, -30d, and -15a contributes to pathogenesis of prostate cancer by targeting Bmi-1.
abstract: Prostate cancer is the second leading cause of cancer-related deaths of men. Bmi-1, a member of PcG family of proteins, has been implicated in the pathogenesis of prostate cancer, and disturbed profile of microRNAs (miRNAs) has been found in prostate cancer tissues. How Bmi-1 is regulated by miRNAs is unclear. In this study, we screened 18 miRNAs that potentially repress the expression of Bmi-1 using a dual luciferase system and found that 12 miRNAs could bind with the 3'-untranslated region of Bmi-1 mRNA. Using qRT-PCR, we found that expression of miR-221, -15a, and -30d was significantly reduced in prostate cancer tissues. Subsequent functional study indicated that miR-221 and miR-30d can repress prostate cancer cell proliferation, and this effect can be partially rescued by Bmi-1 overexpression. Our study constructs the relation between downregulated miR-221 and miR-30d and prostate cancer pathogenesis. These results indicate that miR-221 and miR-30d are candidate tumor suppressor miRNAs in prostate cancer and therefore serve as potential clinical classification markers and therapeutic targets for human prostate cancer.
authors.affiliation: Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 2000127, China. weixuerh@sohu.com.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Xuan
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
authors.forename: Jiahua
authors.initials: J
authors.lastname: Pan
authors.forename: Jianjun
authors.initials: J
authors.lastname: Sha
authors.forename: Baijun
authors.initials: B
authors.lastname: Dong
authors.forename: Yiran
authors.initials: Y
authors.lastname: Huang
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D035683:MicroRNAs; D063150:Polycomb Repressive Complex 1; C069077:BMI1 protein, human; C505361:MIRN15 microRNA, human; C525709:MIR221, human; C546086:MIRN30b microRNA, human