Inhibition of PC4 radiosensitizes non‐small cell lung cancer by transcriptionally suppressing XLF

Positive cofactor 4 (PC4) participates in DNA damage repair and involved in nonhomologous end joining (NHEJ). Our previous results demonstrated that knockdown of PC4 downregulated the expression of XRCC4‐like factor (XLF) in esophageal squamous cell carcinoma. However, the mechanism how PC4 regulates the expression of XLF remains unclear. Here, we found that knockdown of PC4 increased radiosensitivity of non‐small cell lung cancer (NSCLC) both in vivo and in vitro. Furthermore, we found that PC4 knockdown downregulated the expression of XLF, whereas recovering XLF expression restored radioresistance in the PC4‐knockdown NSCLC cells. In addition, PC4 knockdown inhibited XLF expression by transcriptionally suppressing of XLF. Moreover, PC4 expression correlated with radiosensitivity and was an independent prognostic factor of progression‐free survival (PFS) in patients with NSCLC. These findings suggest that PC4 could be used as a promising therapeutic target for NSCLC.