Inhibition of PRPF19 impairs oncogenesis, radioresistance and DNA damage repair in cervical cancer

Background: Cervical cancer (CC) is one prevalent and lethal gynecological malignancy. Pre-mRNA-processing factor 19 (PRPF19) has been implicated in the progression of multiple cancers and shown to play a role in modulating the DNA damage response. However, the specific regulatory effects of PRPF19 and its associated pathways in the development of CC remain poorly understood. Methods: The protein expressions were inspected through western blot. The survival fraction and the number of colonies were examined through colony formation assay. The fluorescence intensity of gamma-histone H2A family member X (gamma H2AX) was verified through Immunofluorescence (IF) assay. The cell invasion and migration were tested through Transwell assay. Results: In this study, data from the Gene Expression Profiling Interactive Analysis (GEPIA) and User-friendly Analysis Tool for Cancer Gene Expression Data (UALCAN) online databases were analyzed, and the findings revealed significant overexpression of PRPF19 in cervical squamous cell carcinoma (CESC) tissues. Additionally, we confirmed elevated PRPF19 expression in CC, with the inhibition of PRPF19 increasing the sensitivity of CC cells to X-ray treatment. Furthermore, PRPF19 knockdown enhanced DNA damage following X-ray exposure, as evidenced by increased gamma H2AX fluorescence intensity and reduced levels of p-DNA-protein kinase (PK) and Rad51 recombinase (Rad51). PRPF19 suppression also inhibited cell migration and invasion. Mechanistically, PRPF19 promoted activation of the Sarcoma (Src)-Yes-associated protein 1 (YAP1) pathway by downregulating p-Src/Src and YAP1 levels. Conclusions: PRPF19 inhibition impairs oncogenesis, reduces radioresistance and disrupts DNA damage repair in CC, partly through modulation of the Src-YAP1 pathway, thereby supporting PRPF19 as one prospective bio-target for CC treatment.