title: microRNA-32 induces radioresistance by targeting DAB2IP and regulating autophagy in prostate cancer cells.
abstract: The aberrant expression of microRNAs (miRNAs/miRs) has been found in numerous cancer types. miR-32 is an oncomiR in prostate cancer (PCa), however, the mechanisms by which miR-32 functions as a regulator of radiotherapy response and resistance in PCa are largely unknown. In the present study, it was found that DAB2 interacting protein (DAB2IP), the miR-32-dependent tumor-suppressor gene, was downregulated and induced autophagy and inhibited radiotherapy-induced apoptosis in PCa cells. miR-32 expression was upregulated or overexpressed in PCa, and miR-32 inhibited DAB2IP expression through a direct binding site within the DAB2IP 3' untranslated region. miR-32 mimics enhanced tumor cell survival and decreased radiosensitivity in the PCa cells, which were reversed by miR-32 inhibitor. Flow cytometric analysis revealed that overexpressed miR-32, consistent with the DAB2IP-knockdown results, reduced ionizing radiation (IR)-induced cell apoptosis, which was restored by 4 nM brefeldin A treatment. More significantly, the overexpression of miR-32 and the knockdown of DAB2IP enhanced autophagy in the IR-treated PCa cells. miR-32 regulated the expression of autophagy-related proteins, such as DAB2IP, Beclin 1 and Light chain 3β I/II, as well as phosphorylation of S6 kinase and mammalian target of rapamycin. In conclusion, these data provide novel insights into the mechanisms governing the regulation of DAB2IP expression by miR-32 and their possible contribution to autophagy and radioresistance in PCa.
authors.affiliation: Department of Urology, Loudi Central Hospital of Hunan, Loudi, Hunan 417000, P.R. China.
authors.forename: Haiqiu
authors.initials: H
authors.lastname: Liao
authors.affiliation: Department of Orthopaedics, Loudi Central Hospital of Hunan, Loudi, Hunan 417000, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Colorectal Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Urology, Loudi Central Hospital of Hunan, Loudi, Hunan 417000, P.R. China.
authors.forename: Yangming
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Urology, Loudi Central Hospital of Hunan, Loudi, Hunan 417000, P.R. China.
authors.forename: Zhaofa
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Oncology, Loudi Central Hospital of Hunan, Loudi, Hunan 417000, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
keywords: DAB2IP; apoptosis; autophagy; microRNA-32; prostate cancer; radioresistance