title: H19-derived miR-675 contributes to bladder cancer cell proliferation by regulating p53 activation.
abstract: Long noncoding RNA 19 (H19) has been shown to promote bladder cancer cell proliferation and metastasis. However, little is known about how miR-675, mature product of H19, contributes to bladder cancer cell proliferation. In this study, we first evaluated the expression of miR-675 in bladder cancer tissues by quantitative real-time PCR (qRT-PCR) and defined its biological functions by flow cytometry and Western blotting. We found that miR-675 expression levels were remarkably increased in bladder cancer tissues as compared with adjacent noncancerous tissues or normal bladder tissue from health donors; moreover, enhanced miR-675 expression was also observed in bladder cancer cell lines. Ectopic expression of H19 significantly increased bladder cancer cell proliferation and miR-675 expression in vitro. Furthermore, overexpression of miR-675 promoted bladder cancer cell proliferation, while suppression of miR-675 induced G1 phase cell cycle arrest and promoted cell apoptosis. Western blotting analysis further identified that miR-675 inhibited p53 activation, decreased the ratio of Bax/Bcl-2 and cyclin D1 expression in bladder cancer cells; those effects may result in the abnormal proliferation of bladder cancer cells. In conclusion, abnormal enhanced miR-675 expression increases bladder cancer growth by regulating p53 activation, and thus may be helpful in the development of effective treatment strategies for bladder cancer.
authors.affiliation: State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|Department of Urology, Subei Hospital, Yangzhou University, Yangzhou, China.
authors.forename: Changkun
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Urology, Subei Hospital, Yangzhou University, Yangzhou, China.
authors.forename: Zhouguang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Clinical Center of Reproductive Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Jianzheng
authors.initials: J
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Aiming
authors.initials: A
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. lmy111105@163.com.
authors.forename: Zengjun
authors.identifier: http://orcid.org/0000-0002-5085-6208
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D000199:Actins; C530104:CCND1 protein, human; C094335:H19 long non-coding RNA; C548379:MIRN675 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1
keywords: Bladder cancer; H19; Proliferation; miR-675; p53