Silencing UCHL3 enhances radio-sensitivity of non-small cell lung cancer cells by inhibiting DNA repair.

UCHL3 belongs to the UCH family and is involved in multiple biological processes. However, the biological functions and underlying mechanisms of action of UCHL3 in radio-sensitivity of non-small cell lung cancer (NSCLC) remain unknown. Here, we reported that the expression of UCHL3 was significantly up-regulated in NSCLC tissues and cell lines, and associated with poor prognosis of NSCLC patients. The expression of UCHL3 of NSCLC cells was increased after exposure to ionizing radiation (IR). Moreover, we found that knockdown of UCHL3 enhanced the radio-sensitivity of NSCLC cells both in vitro and in vivo. Furthermore, γH2AX foci staining and Western blot analysis showed that knockdown of UCHL3 increased IR-induced DNA damage. Knockdown of UCHL3 in NSCLC cells decreased homologous recombination (HR) repair efficiency and RAD51 foci formation. Collectively, our study revealed that knockdown of UCHL3 enhanced the radio-sensitivity of NSCLC cells and increased IR-induced DNA damage via impairing HR repair.