MicroRNA-608 inhibits proliferation of bladder cancer via AKT/FOXO3a signaling pathway

Molecular Cancer

Research

Bo Xie¹  Alin Ji²  Zhen Liang³  Zhenghui Hu³  Xin Xu³  Liping Xie³  Xiao Wang³  Shuai Meng³  Yi Zhu³  Jian Wu³  Xiangyi Zheng³  Yiwei Lin³  Ben Liu³  Shiqi Li³ 

[1] Department of Urology, TongDe Hospital of Zhejiang Province, Hangzhou, China;Department of Urology, Zhejiang Provincial People’s Hospital, Hangzhou, China;Department of Urology, the First Affiliated Hospital, Zhejiang University, School of Medicine, 79, Qingchun Road, 310003, Hangzhou, Zhejiang, China;

关键词: Bladder cancer;    Proliferation;    MicroRNA-608;    FLOT1;   

DOI  :  10.1186/s12943-017-0664-1

 received in 2016-11-17, accepted in 2017-05-18,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundCurrent evidence indicates that miR-608 is widely down-regulated in various malignant tumors including liver cancer, colon cancer, lung cancer and glioma, and acts as a tumor suppressor by inhibiting cell proliferation, invasion and migration or by promoting apoptosis. The specific biological function of miR-608 in bladder cancer is still unknown.MethodsqRT-PCR and Chromogenic in Situ Hybridization (CISH) was conducted to assess the expression of miR-608 in paired BCa tissues and adjacent non-tumor bladder urothelial tissues. Bisulfite sequencing PCR was used for DNA methylation analysis. CCK-8, colony formation and flow cytometry assays were performed, and a xenograft model was studied. Immunohistochemistry staining was performed with peroxidase and DAB. The target of miR-608 was validated with a dual-luciferase reporter assay, quantitative RT-PCR, and Western blotting.ResultsmiR-608 is frequently down-regulated in human BCa tissues. The methylation status of CpG islands is involved in the regulation of miR-608 expression. Overexpression of miR-608 inhibits the proliferation and tumorigenesis of BCa cells in vitro and in vivo. Additionally, up-regulation of miR-608 in BCa cells induces G1-phase arrest through AKT/FOXO3a signaling. In contrast, down-regulation of miR-608 promotes proliferation and cell cycle progression in BCa cells. Moreover, the expression of FLOT1 was directly inhibited by miR-608, the down-regulation of FLOT1 induced by siFLOT1 could be significantly reversed by miR-608 inhibitor. Similarly, the up-regulation of FLOT1 by FLOT1 overexpression plasmid (pFLOT1) could also reverse the suppressed cell proliferation caused by miR-608.ConclusionsmiR-608 is a potential tumor suppressor in BCa, and the restoration of miR-608 might be a promising therapeutic option for BCa.

【 授权许可】

CC BY   
© The Author(s). 2017