SPI1 transcriptionally regulates WDR66 to promote oxaliplatin resistance in esophageal squamous cell carcinoma

Background Spleen focus forming virus proviral integration oncogene 1 (SPI1) and WD repeat domain 66 (WDR66) are key regulators of esophageal squamous cell carcinoma (ESCC) progression, yet their roles in oxaliplatin (L-OHP) resistance remain unclear. This study aims to investigate the roles of SPI1 and WDR66 in L-OHP resistance and elucidate the underlying molecular mechanisms in ESCC. Methods The gene expression omnibus (GEO) database and the university of alabama at birmingham cancer data analysis portal (UALCAN) website were used to download ESCC-related datasets and validate gene expression. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot were used to detect mRNA and protein levels. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were used to investigate the binding of transcription factors to gene promoters. Cell counting kit-8 (CCK-8), flow cytometry, and transwell assays were used to evaluate cell viability, apoptosis, and cell migration and invasion, respectively. Results WDR66 was highly expressed in ESCC-related datasets ( P < 0.001), and its high expression in ESCC tumor tissues and resistant cells was confirmed experimentally ( P < 0.001). SPI1 positively regulated the transcription of WDR66 and was highly expressed in ESCC-related datasets, tumor tissues, and cells ( P < 0.001). Knockdown of WDR66 or SPI1 reduced the viability of ESCC resistant cells ( P < 0.01), increased apoptosis ( P < 0.001), upregulated cleaved caspase-3 (Cl.cas 3) and Bcl-2-associated X protein (Bax) expression, downregulated B-cell lymphoma 2 (Bcl-2) expression ( P < 0.001), and decreased cell migration and invasion ( P < 0.001). Moreover, overexpression of WDR66 partially reversed the effects induced by SPI1 knockdown ( P < 0.001). Conclusion The transcription factor SPI1 promoted WDR66 expression, thereby enhancing drug resistance in ESCC cells and providing a new perspective on the mechanisms underlying ESCC chemoresistance.