Effects of USP7 on radiation sensitivity through p53 pathway in laryngeal squamous cell carcinoma

Abstract

The relationship between ubiquitin specific protease 7 (USP7) and radio-sensitivity in laryngeal squamous cell carcinoma (LSCC) has not been reported yet. Using gene chip and Label-Free mass spectrometry, we found that USP7 was significantly increased both in radioresistant LSCC patients and LSCC cells receiving irradiation. Since p53 is the most important downstream gene of USP7 and is frequently mutated in LSCC, we investigated the effects of USP7 on radioresistance of LSCC cells with or without p53 mutation. We found that knockdown of USP7 increased the radio-sensitivity in p53-mutated LSCC cells, while inhibiting the radio-sensitivity in p53-wild type cells. Knockdown of USP7 significantly inhibited the expression of the p53 and p53 pathway. Overexpressing endogenous p53 by CRISPR/dCas9 could reverse the effects of USP7 on radiosensitivity both in vitro and in vivo. Our results demonstrated the irradiation-induced USP7 led to radioresistance in p53-mutated LSCC cells but radio-sensitivity in p53-wild type cells. Therefore, the clinical application of USP7 inhibitors may improve the effects of radiotherapy in LSCC with p53 mutations and reduce the side effects on surrounding normal tissues without p53 mutation.