Role of SOX5-mediated DNA repair pathways in the emergence of cisplatin resistance in hypopharyngeal squamous cell carcinoma
OBJECTIVE To explore the effect of SOX5 on cisplatin(DDP)resistance in hypopharyngeal carcinoma(HPC)and elucidate its mechanism.METHODS The expression and enrichment pathway of SOX5 in HPC tissues were analyzed.The upstream transcription factor FOXM1 of SOX5 was predicted,the expression of FOXM1 in HPC tissues examined and binding relationship between the two was analyzed by dual luciferase and ChIP assays.The expression levels of SOX5 and FOXM1 in HPC cells were detected by quantitative polymerase chain reaction(qPCR).CCK-8 was utilized for detecting cell viability.Cell proliferation was detected by 5-ethynyl-2-deoxyuridine(EdU),apoptosis by flow cytometry,DNA damage by comet assay and expression of γ-H2AX by immunofluorescence.Non-homologous DNA end joining(NHEJ)report analysis was utilized for detecting DNA repair efficiency and WB for detecting the expression of DNA damage repair-related proteins.The expression of related genes was detected by immunohistochemistry.An animal model was constructed for exploring the effect of FOXM1 expression on HPC tumor growth.RESULTS SOX5 was highly expressed in HPC.Overexpression of SOX5 mediated DNA damage repair and promoted DDP resistance in HPC.As an upstream transcription factor of SOX5,FOXM1 was highly expressed in HPC.Restoration experiments indicated that a knockdown of FOXM1 could attenuate the effect of SOX5 overexpres-sion on DDP resistance of HPC through DNA damage repair.In vivo assays showed that a knockdown of FOXM1 expression plus DDP dosing could significantly retard the growth of xenograft tumors.CONCLUSION FOXM1/SOX5 axis mediates DNA dam-age repair to promote HPC DDP resistance.The results of this study may help to optimize therapeutic strategies after chemo-therapy resistance.
NETL
NSTL
万方数据
