Study On The Mechanism Of CircRNA HMGB3 Regulating The Proliferation,metastasis And Radiotherapy Resistance Of Esophageal Cancer

Objective: Radiotherapy is an important treatment for esophageal cancer.However,the existence of therapeutic resistance largely limits therapeutic efficacy.Therefore,there is an urgent need to identify biomarkers to predict and improve chemoradiotherapy response.Circ RNAs regulate tumor initiation,progression,proliferation,migration,invasion,and sensitivity to therapy.This study hopes to explore the molecular mechanism of circ RNA in esophageal cancer radiotherapy resistance,and provide new ideas and guidance for improving the clinical efficacy of esophageal cancer.Methods: RNA-seq was used to sequence esophageal cancer clinical samples,and q RT-PCR experiment was used to detect the expression of circ RNA HMGB3 in esophageal cancer and paired adjacent samples.After RNAi gene silencing technology down-regulated circ RNA HMGB3,the effect of circ RNA HMGB3 on the proliferation of esophageal cancer cells was detected by CCK8 experiment and subcutaneous tumor model in nude mice,and the effect of circ RNA HMGB3 on the metastatic ability of esophageal cancer cells was detected by Transwell assay.The online Starbsae and DIANA tools were used to analyze the targeting effects of circ RNA HMGB3 on mi R-1179 and mi R-1179 on HMGB3,and were verified by dual luciferase and RNA pull-down.In addition,irradiation was performed in esophageal cancer cells that stably down-regulated circ RNA HMGB3,and DNA damage proteins were detected by Western-blot assay to clarify the molecular mechanism of circ RNA HMGB3 on esophageal cancer resistance to esophageal cancer radiotherapy.Results: Compared with adjacent normal tissues,circ RNA HMGB3 was highly expressed in esophageal cancer tissues.After silencing the expression of circ RNA HMGB3,the proliferation,tumorigenic and metastatic abilities of esophageal cancer cells were inhibited.Online database analysis combined with dual luciferase experiments and RNA pull-down experiments confirmed that circ RNA HMGB3 and HMGB3 had competitive binding to mi R-1179,and silencing circ RNA HMGB3 could down-regulate the expression of HMGB3.Meanwhile,under the background that irradiation can enhance DNA damage signals,silencing circ RNA HMGB3 can enhance the killing of esophageal cells by irradiation,and at the same time downregulate the expression of DNA damage-related h TERT.Conclusion: The circ RNA HMGB3 can promote the progression,metastasis and radiotherapy resistance of esophageal cancer,and is a potential target for clinical treatment of esophageal cancer.