Inhibition of PC 4 radiosensitizes non‐small cell lung cancer by transcriptionally suppressing XLF

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