Rps15a Imparts Chemoresistance by Regulating Cd44 Expression and Cell Stemness in Esophageal Squamous Cell Carcinoma

Chemotherapy is one of the effective ways to treat esophageal squamous cell carcinoma (ESCC), but the development of chemoresistance during chemotherapy lowers drug efficacy. Although previous studies have shown that the ribosomal protein S15A (RPS15A) involved in the progression and overall survival of malignancies, its function in chemoresistance is unknown. This study sought to elucidate the function of RPS15A in chemoresistance in ESCC. Our results show that knocking down or overexpressing RPS15A in ESCC cell lines can significantly change the sensitivity of chemotherapeutic drugs and affect cisplatin-induced apoptosis. Moreover, an increase in chemotherapeutic drug concentration leads to increased expression of RPS15A and CD44 proteins. When we utilized the ESCC cisplatin-resistant cell line to corroborate our findings, we found that the levels of RPS15A and CD44 proteins were substantially greater in daughter than parental cells. Subsequent experiments indicated that RPS15A modulated chemoresistance by controlling the expression of CD44 and the cell stemness in ESCC. Hence, our data suggest that RPS15A participates in the chemoresistance in ESCC by controlling the expression of CD44 and regulating cell stemness. Taken together, our study provides plausible mechanisms for RPS15A-mediated chemoresistance in ESCC cells and suggests that the inhibition of the RPS15A/CD44 pathway may be a potential target for improving chemotherapy efficacy.