Experimental Study Of UBQLN2 In Radiosensitivity Regulation Of Esophageal Squamous Cell Carcinoma

Objective: To study the effect of UBQLN2 gene expression on the radiosensitivity of esophageal squamous cell carcinoma and explore its possible mechanism.Methods: The expression of UBQLN2 in esophageal squamous cell carcinoma Ec109 and KYSE-30 cell lines was down-regulated by siRNA transfection technology;the effects of downregulation of UBQLN2 expression on the radiosensitivity of ESCC(esophageal squamous cell carcinoma)were detected by cell clone formation experiments and western.Downstream target genes of UBQLN2 gene were screened by RNA-seq.The downstream target genes of UBQLN2 and its effects on radiosensitivity of esophageal squamous cell carcinoma were explored by western blot experiments,cell clone formation experiments and specific small molecule inhibitors.Results :(1)Successfully down-regulated the expression levels of UBQLN2 genes in two ESCC(Ec109,KYSE-30)cell lines.It was found that down-regulating the expression of UBQLN2 increased the radiosensitivity of ESCC cells and reduced the expression level of DNA damage repair enzyme DNA-PKcs.(2)RNA-seq experiments and bioinformatics analysis were performed on Ec109 cells after down-regulated the expression level of UBQLN2,p38 / MAPK was identified as the downstream target of UBQLN2 for further analysis.(3)Western blot experiments verified that after down-regulating UBQLN2,the p38 / MAPK pathway was activated.(4)Using p38 inhibitor SB203580 to inhibit the p38 / MAPK pathway can reverse the radiosensitization effect caused by UBQNL2 downregulation(P <0.05).Conclusion: Down-Down-regulating the expression level of UBQLN2 gene can increase the radiosensitivity of esophageal squamous carcinoma cells via activating the p38 / MAPK pathway.