Deregulation of circRNA hsa_circ_0009109 promotes tumor growth and initiates autophagy by sponging miR-544a-3p in gastric cancer
Weiwei Zhang1
Qian Yang2
Dongchen Qian3
Keli Zhao4
Chenxue Tang5
Shaoqing Ju5
1.Department of Laboratory Medicine,Affiliated Hospital of Nantong University,Nantong,Jiangsu,P.R.China;Research Center of Clinical Medicine,Affiliated Hospital of Nantong University,Nantong,Jiangsu,P.R.China2.Center of Clinical Laboratory,First Affiliated Hospital of Soochow University,Suzhou,Jiangsu,P.R.China3.Department of Anesthesia and Surgery,Affiliated Hospital of Nantong University,Nantong,Jiangsu,P.R.China4.Key Laboratory of Interdisciplinary Research,Institute of Biophysics,Chinese Academy of Sciences,Beijing,P.R.China5.Department of Laboratory Medicine,Affiliated Hospital of Nantong University,Nantong,Jiangsu,P.R.China
摘要：Background:Autophagy death of cancer cells is detrimental to apoptosis induced by therapeutic drugs,which promotes tumor pro-gression 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 reduc-tion 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 ef-fect 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.
机标关键词：circrnagrowthcancertumorautophagyderegulationgastricinitiates
论文发表日期：2024-10-30
在线出版日期：2026-07-17（本平台首次上网日期，不代表文献的发表时间）
页数：12( 447-458 )
英文信息