MicroRNA-182 plays an onco-miRNA role in cervical cancer.
By: Tao Tang, Hoi Kin Wong, Wenyi Gu, Mei-Yung Yu, Ka-Fai To, Chi Chiu Wang, Yick Fu Wong, Tak Hong Cheung, Tony Kwok Hung Chung, Kwong Wai Choy

Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
2012-10-18; doi: 10.1016/j.ygyno.2012.12.043
Abstract

OBJECTIVES: The purposes of this study were to identify aberrantly expressed miRNAs and investigate their pathogenic roles in cervical cancer. METHODS: miRNA expression was assessed in cervical cancer cell lines, micro-dissected normal cervical epithelium cells and primary cervical carcinoma by TaqMan RT-PCR. Spatial expression of miR-182 in cervical carcinoma and normal cervix was explored by in situ hybridization. HeLa xenograft mice model was used for evaluation of the effect on tumor growth of miR-182 inhibitor. Western blot, flow cytometry and gene expression analysis were used for identification of the functional role of miR-182 in HeLa cells. RESULTS: Two up-regulated (miR-182 and -183) and nine down-regulated (miR-211, 145, 223, 150, 142-5p, 328, 195, 199b, 142-3p) microRNAs were consistently identified in cervical cancer cell lines. Further investigation confirmed the most up-regulated miRNA (miR-182) was significantly elevated in primary cervical carcinoma and discovered a significant correlation between the increased expression of miR-182 and advanced stages of cervical cancer. In HeLa xenograft mouse model, we demonstrated that inhibition of the miR-182 could exert the effect of tumor growth regression. Western blot, flow cytometry and pathway analysis for the HeLa cells with miR-182 over/down-expression in vitro showed that miR-182 was involved in apoptosis and cell cycle pathways, it also associated with the regulation of FOXO1. CONCLUSIONS: Our findings indicated that miR-182 plays an onco-miRNA role in cervical cancer and its alteration is associated with cervical cancer pathogenesis by disrupting cell proliferation.



Copyright © 2012. Published by Elsevier Inc.

PMID:23313739






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