The Mechanism Of RPS15A In Chemotherapy Resistance Of Esophageal Squamous Cell Carcinoma Cells

Objective: Esophageal squamous cell carcinoma(ESCC)is the main histological subtype of esophageal cancer and has a high incidence in China.And it also has a high mortality rate and a poor prognosis.At present,chemotherapy is one of the most effective ways to treat ESCC.But the development of drug resistance during chemotherapy is one of the most main and important reasons for the low survival rate of patients after treatment.The ribosomal protein S15A(RPS15A)is a member of the ribosomal protein family.It has been reported that it plays an important role in the oncogenesis and development of various tumors such as gastric cancer and breast cancer,and is related to angiogenesis and the EMT process of tumors.However,the role and molecular mechanism of RPS15 A in tumor resistance need to be further explored.Therefore,this study aims to explore the role and molecular mechanism of RPS15 A in the process of developing acquired resistance in ESCC cells.In order to provide targets,experimental basis,and theoretical support for the development of new therapeutic strategies for Esophageal squamous cell carcinoma.Methods: The sensitivity of ESCC drug-resistant cell line to different chemotherapeutic drugs was verified by the experiment methods of CCK-8 and clone formation.Drug resistance was detected by the expression of related genes by RT-q PCR and Western blot.Construction of RPS15 A knockdown and overexpression were steadily transfected into ESCC cells using lentiviral vectors.CCK-8 assay,clone formation assay and Annexin V/PI double staining were used to research the influence of RPS15 A in the resistance of ESCC cells.CD44 positive and CD44 negative cells were isolated from ESCC cells by MACS,which was verified by RT-q PCR and Western blot.Western blot and bioinformatics analysis were performed on the relationship between RPS15 A and CD44 and Fox O1,the key molecules of tumor resistance,using the TCGA database.Conclusions: Our results suggest that knocking down or overexpressing RPS15 A in ESCC cell lines can significantly change the sensitivity of chemotherapeutic drugs and could affect chemotherapeutic drug-induced apoptosis.When we utilize ESCC cisplatin-resistant cell lines to make a validation,the result was also similar to that on ESCC parent cells.Mechanically,RPS15 A can mediate the acquired resistance of ESCC cells by regulating the expression of CD44.Significance: This study found that RPS15 A is involved in regulating the sensitivity of ESCC cells to chemotherapeutic drugs.And we discovered a new molecular mechanism that regulates the generation of ESCC acquired resistance,which once again confirmed that RPS15 A may be a pro-oncogenic factor for ESCC.This research provides a potential target for the treatment of ESCC and provides a basis for a new treatment strategy for ESCC in clinical.