microRNA‑32 induces radioresistance by targeting DAB2IP and regulating autophagy in prostate cancer cells

Liao,Haiqiu; Xiao,Yang; Hu,Yingbin; Xiao,Yangming; Yin,Zhaofa; Liu,Liang

doi:10.3892/ol.2015.3551

microRNA‑32 induces radioresistance by targeting DAB2IP and regulating autophagy in prostate cancer cells

Authors:
- Haiqiu Liao
- Yang Xiao
- Yingbin Hu
- Yangming Xiao
- Zhaofa Yin
- Liang Liu
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Affiliations: Department of Urology, Loudi Central Hospital of Hunan, Loudi, Hunan 417000, P.R. China, Department of Orthopaedics, Loudi Central Hospital of Hunan, Loudi, Hunan 417000, P.R. China, Department of Colorectal Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China, Department of Oncology, Loudi Central Hospital of Hunan, Loudi, Hunan 417000, P.R. China
Published online on: July 30, 2015 https://doi.org/10.3892/ol.2015.3551
Pages: 2055-2062
Copyright: © Liao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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