IFI6 regulates cisplatin resistance and antitumor effects in tongue squamous cell carcinoma

CHENG Hui-lin; XIA Xin; HUANG Zhuo-shan

doi:10.13820/j.cnki.gdyx.20250005

Abstract：Objective To explore the mechanism by which IFI6 regulates cisplatin resistance and its anti-tumor effects in tongue squamous cell carcinoma(TSCC).Methods Clinical sample analysis was performed to investigate the relationship between IFI6 expression and cisplatin resistance,clinicopathological characteristics,and prognosis in TSCC patients.The expression levels of IFI6 in TSCC cell lines were silenced and overexpressed to determine its effect on cispla-tin resistance,migration,and invasion abilities of TSCC cells.Immunofluorescence and laser confocal microscopy were used to detect IFI6 localization within cells.Western blot(WB)was utilized to examine the relationship between IFI6 ex-pression and the expression of key target genes Caspase3 and Caspase9 involved in the mitochondrial-dependent apoptosis pathway.Results IFI6 expression was significantly higher in TSCC tissues compared to adjacent non-tumor tissues,with even higher expression in chemotherapy-resistant tumors compared to chemotherapy-sensitive tumors.Preliminary survival curve analysis of clinical follow-up data indicated that high IFI6 expression was associated with poor prognosis(P＜0.05).Silencing IFI6 enhanced cisplatin sensitivity,reduced cell migration,proliferation,and invasion abilities.Conversely,overexpressing IFI6 increased cisplatin resistance and enhanced migration,proliferation,and invasion capa-bilities of TSCC cells.Laser confocal microscopy revealed that IFI6 was primarily located in mitochondria.In the TSCC cell line CAL27 and its cisplatin-resistant subline CAL27-re,overexpression and silencing of IFI6 demonstrated a posi-tive correlation between IFI6 expression and Caspase3/9 activity by WB analysis.Conclusion IFI6 may enhance mito-chondrial membrane stability and negatively regulate the activity of apoptosis-related proteins,thereby exerting anti-ap-optotic effects,promoting cisplatin resistance,and enhancing migration and invasion abilities of TSCC cells.