MicroRNA-499 serves as a sensitizer for lung cancer cells to radiotherapy by inhibition of CK2α-mediated phosphorylation of p65

Mol Ther Oncolytics. 2021 Apr 3:21:171-182. doi: 10.1016/j.omto.2021.03.016. eCollection 2021 Jun 25.

Abstract

The present study aimed to define the tumor-suppressive role of microRNA-499 (miR-499) in lung cancer cells and its underlying mechanism. First, qRT-PCR analysis revealed poor expression of miR-499 in clinical samples and cell lines of lung cancer. Next, we performed loss- and gain-of-function experiments for the expression of miR-499 in lung cancer cells exposed to irradiation (IR) to determine the effect of miR-499 expression on cell viability and apoptosis as well as tumor growth. Results showed that overexpression of miR-499 inhibited cell viability, enhanced the radiosensitivity of lung cancer cells, and promoted cell apoptosis under IR. Furthermore, CK2α was verified to be a target of miR-499, and miR-499 was identified to repress p65 phosphorylation by downregulating CK2α expression, which ultimately diminished the survival rate of lung cancer cells under IR. Collectively, the key findings of the study illustrate the tumor-inhibiting function of miR-499 and confirmed that miR-499-mediated CK2α inhibition and altered p65 phosphorylation enhances the sensitivity of lung cancer cells to IR.

Keywords: casein kinase 2 alpha; lung cancer; microRNA-499; p65 phosphorylation; radiotherapy sensitivity.