Deregulation of circRNA hsa_circ_0009109 promotes tumor growth and initiates autophagy by sponging miR-544a-3p in gastric cancer  

作　　者：Weiwei Zhang Qian Yang Dongchen Qian Keli Zhao Chenxue Tang Shaoqing Ju 

机构地区：[1]Department of Laboratory Medicine,Affiliated Hospital of Nantong University,Nantong,Jiangsu,P.R.China [2]Research Center of Clinical Medicine,Affiliated Hospital of Nantong University,Nantong,Jiangsu,P.R.China [3]Center of Clinical Laboratory,First Affiliated Hospital of Soochow University,Suzhou,Jiangsu,P.R.China [4]Department of Anesthesia and Surgery,Affiliated Hospital of Nantong University,Nantong,Jiangsu,P.R.China [5]Key Laboratory of Interdisciplinary Research,Institute of Biophysics,Chinese Academy of Sciences,Beijing,P.R.China

出　　处：《Gastroenterology Report》2024年第1期79-90,共12页胃肠病学报道(英文)

基　　金：supported by the National Natural Science Foundation of China[nos 82272411,82072363];Jiangsu Innovative and Entrepreneurial Talent Programme[JSSCBS20211602];PhD Research Startup Foundation of Affiliated Hospital of Nantong University[Tdb2011];Postdoctoral Research Foundation of Affiliated Hospital of Nantong University[BSH202110];Scientific Research Project of Nantong Municipal Health Commission[QN2022015],Nantong Basic Research Program[JC12022007];Grants from Jiangsu Provincial Research Hospital[YJXYY202204-YSC28].

摘　　要：Background:Autophagy death of cancer cells is detrimental to apoptosis induced by therapeutic drugs,which promotes tumor progression to a certain extent.Increasing reports have demonstrated the regulatory role of circular RNAs(circRNAs)in autophagy.Here,we aimed to determine the role of hsa_circ_0009109 in autophagy in gastric cancer(GC).Methods:The effects of hsa_circ_0009109 on autophagy were examined using quantitative real-time polymerase chain reaction(qPCR),transmission electron microscopy,Western blot,and immunofluorescence.The mechanism of hsa_circ_0009109 regulating the miR-544a-3p/bcl-2 axis was analysed using fluorescence in situ hybridization,dual-luciferase reporter,and rescue experiments.Results:Functional testing indicated that hsa_circ_0009109 was significantly down-expressed in GC tissues and cell lines.A reduction in cytoplasmic-derived hsa_circ_0009109 could promote GC progression by accelerating cell proliferation,enhancing migration and invasion,inhibiting apoptosis,and accelerating the cell cycle progression.Besides,hsa_circ_0009109 was found to exert the effect of an autophagy inhibitor such as 3-Methyladenine(3-MA),which was manifested by the weakening of the immunofluorescence of LC3B and the reduction in autophagy-related proteins after overexpression of hsa_circ_0009109,while increased autophagosomes were observed after interference with hsa_circ_0009109.Subsequently,the crosstalk between hsa_circ_0009109 and miR-544a-3p/bcl-2 was verified using dual-luciferase reporter assay.The autophagy status was altered under the regulation of the hsa_circ_0009109-targeted miR-544a-3p/bcl-2 axis.Conclusions:The hsa_circ_0009109 mediated a novel autophagy regulatory network through targeting the miR-544a-3p/bcl-2 axis,which may shed new light on the exploration of therapeutic targets for the clinical treatment of GC.

关 键 词：hsa_circ_0009109 circRNA AUTOPHAGY miR-544a-3p gastric cancer 

分 类 号：R735.2[医药卫生—肿瘤]