J Cancer 2020; 11(21):6356-6364. doi:10.7150/jca.48216

Research Paper

MicroRNA-29b-3p enhances radiosensitivity through modulating WISP1-mediated mitochondrial apoptosis in prostate cancer cells

Aihong Mao1,2#, Jinzhou Tang1#, Deping Tang3, Fang Wang2, Shiqi Liao1, Hongxia Yuan1, Caiping Tian1, Chao Sun2, Jing Si2, Hong Zhang2✉, Xiaojun Xia1,4✉

1. Gansu Provincial Academic Institute for Medical Research, Lanzhou, China.
2. Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
3. School of Chemical & Biological Engineering, Lanzhou Jiaotong University, Lanzhou 730070, PR China.
4. Gansu Provincial Cancer Hospital, Lanzhou, China.
#These authors contributed equally to this work.

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Citation:
Mao A, Tang J, Tang D, Wang F, Liao S, Yuan H, Tian C, Sun C, Si J, Zhang H, Xia X. MicroRNA-29b-3p enhances radiosensitivity through modulating WISP1-mediated mitochondrial apoptosis in prostate cancer cells. J Cancer 2020; 11(21):6356-6364. doi:10.7150/jca.48216. Available from http://www.jcancer.org/v11p6356.htm

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Abstract

Radiotherapy is frequently applied for clinically localized prostate cancer while its efficacy could be significantly hindered by radioresistance. MicroRNAs (miRNAs) are important regulators in mediating cellular responses to ionizing radiation (IR), and strongly associate with radiosensitivity in many cancers. In this study, enhancement of radiosensitivity by miR-29b-3p was demonstrated in prostate cancer cell line LNCaP in vitro. Results showed that miR-29b-3p expression was significantly upregulated in response to IR from both X-rays and carbon ion irradiations. Knockdown of miR-29b-3p resulted in radioresistance while overexpression of miR-29b-3p led to increased radiosensitivity (showing reduced cell viability, suppressed cell proliferation and decreased colony formation). In addition, miR-29b-3p was found to directly target Wnt1-inducible-signaling protein 1 (WISP1). Inhibition of WISP1 facilitated the mitochondrial apoptosis pathway through suppressing Bcl-XL expression while activating caspase-3 and poly (ADP-ribose) polymerase (PARP). The results indicated that miR-29b-3p was a radiosensitizing miRNAs and could enhance radiosensitivity of LNCaP cells by targeting WISP1. These findings suggested a novel treatment to overcome radioresistance in prostate cancer patients, especially those with higher levels of the WISP1 expression.

Keywords: MiR-29b-3p, WISP1, radiosensitivity, apoptosis, prostate cancer