MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1

Tengfei Li; Ji Ma; Xinwei Han; Yongxu Jia; Huifeng Yuan; Shaofeng Shui; Dong Guo

doi:10.1016/j.tranon.2017.12.008

MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1

Transl Oncol. 2018 Apr;11(2):205-212. doi: 10.1016/j.tranon.2017.12.008. Epub 2018 Jan 11.

Authors

Tengfei Li¹, Ji Ma¹, Xinwei Han², Yongxu Jia³, Huifeng Yuan¹, Shaofeng Shui¹, Dong Guo¹

Affiliations

¹ Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, PR China; Interventional Institute of Zhengzhou University, Zhengzhou, 450052, PR China.
² Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, PR China; Interventional Institute of Zhengzhou University, Zhengzhou, 450052, PR China. Electronic address: hanxinwei2016@126.com.
³ Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, PR China.

Abstract

Glioma is the most common cancer in human brain system and seriously threatens human health. miRNA-320 has been demonstrated to be closely correlated with the development of glioma. However, its effect and molecular mechanism underlying radioresistance have not been fully elucidated in glioma. Here, RT-qPCR assay was used to assess the expressions of miR-320 and forkhead box protein M1 (FoxM1) mRNA in glioma tumor tissues and cells. The effects of miR-320, FoxM1 and sirtuin type 1 (Sirt1) on radiosensitivity in glioma cells were evaluated by clone formation assay, apoptosis assay, histone H2AX phosphorylation level (γH2AX) detection and caspase 3 activity analysis, respectively. The direct interaction between miR-320 and FoxM1 was detected by luciferase assay. The protein levels of FoxM1, Sirt1 and γH2AX were measured by western blot assay. We found that miR-320 expression was down-regulated and FoxM1 expression was up-regulated in radioresistant glioma tissues and IR-treated glioma cells. miR-320 overexpression dramatically enhanced radiosensitivity, promoted apoptosis, and improved γH2AX expression and caspase 3 activity in glioma cells. Luciferase reporter assay and western blot assay further validated that miR-320 suppressed FoxM1 expression by directly targeting 3' UTR region of FoxM1. Moreover, miR-320 inhibited Sirt1 expression via targeting FoxM1 in glioma cells. Furthermore, overexpression of FoxM1 and Sirt1 strikingly attenuated miR-320-induced increase of radiosensitivity, apoptosis and γH2AX expression in glioma cells. In conclusion, miR-320 enhanced radiosensitivity of glioma cells through down-regulation of Sirt1 by directly targeting FoxM1.