RHCG inhibition promotes the sensitivity of PIK3CA-mutant non-small lung cancer to PI3K inhibitor.

Abstract

PIK3CA, the gene encoding the catalytic subunit of the PI3K complex, is significantly amplified and mutated in several cancer forms, including non-small cell lung cancer (NSCLC). Although follicular lymphoma and chronic lymphocytic leukemia have been treated clinically with PI3K inhibitors, there are currently no FDA-approved medications targeting PI3K mutations in lung cancer. In this study, by TCGA database analysis, we found that RHCG was highly expressed in PIK3CA-mutated NSCLC and was associated with poor prognosis. Knockdown of RHCG in PIK3CA-mutated NSCLC inhibited cell proliferation and promoted apoptosis, thereby sensitizing cells to PI3K inhibitors. Mechanistically, the knockdown of RHCG acts synergistically with PI3K inhibitors to produce more effective inhibition of AKT and S6RP phosphorylation downstream of PI3K. This finding suggests a potential NSCLC target with PIK3CA mutations.