Knockdown of RNF2 enhances radiosensitivity of lung squamous cell carcinoma cells.

Knockdown of RNF2 enhances radiosensitivity of lung squamous cell carcinoma cells.

Biochem Cell Biol. 2019 Jan 23;:

Authors: Yang J, Yu F, Guan J, Wang T, Liu C, Wang Y, Liu G, Zhu S

Abstract
A previous study has reported that RING finger protein 2 (RNF2) knockdown increases radiosensitivity of esophageal cancer cells both in vitro and in vivo. However, the effect of RNF2 knockdown on radiosensitivity in squamous cell carcinoma (SqCC) remains unknown. NCI-H226 and SK-MES-1 cells were exposed to X-ray irradiation and then RNF2 levels were determined. RNF2 was knocked down and stable transfectants were selected. Radiosensitivity, cell proliferation, apoptosis, cell cycle and γ-H2AX foci formation were evaluated. Interaction among ataxia telangiectasia mutated protein (ATM), mediator of DNA damage checkpoint 1 (MDC1) and H2AX was examined. Xenograft models were used to explore the effect of RNF2 knockdown on radiosensitivity in vivo. The results showed that RNF2 expression was significantly increased by X-ray irradiation. RNF2 knockdown combined with X-ray irradiation markedly inhibited cell proliferation, caused cell cycle arrest at G1 phase and induced cell apoptosis. In addition, RNF2 knockdown enhanced radiosensitivity of SqCC cells, inhibited irradiation-induced γ-H2AX foci formation and impaired the interaction among ATM, MDC1 and H2AX. Furthermore, combination of RNF2 knockdown and X-ray irradiation suppressed tumor growth and promoted tumor cell apoptosis in vivo. RNF2 may be a new therapeutic target to enhance radiosensitivity of lung SqCC cells.

PMID: 30673298 [PubMed - as supplied by publisher]

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