circ_0071653靶向miR-197-3p调控食管鳞状细胞癌的增殖和转移  

circ_0071653 targeted miR-197-3p regulates proliferation and metastasis of esophageal squamous cell carcinoma

作　　者：郑璇 戈艳蕾 甘俊清 金叶 崔逸爽 吴亚男 刘子情 孙国贵 ZHENG Xuan;GE Yan-lei;GAN Jun-qing;JIN Ye;CUI Yi-shuang;WU Ya-nan;LIU Zi-qing;SUN Guo-gui(School of Public Health,North China University of Science and Technology,Tangshan Hebei 063210,China;Dept of Radiotherapy and Chemotherapy,Affiliated Hospital of North China University of Science and Technology;Dept of Hebei Key laboratory of Medical-Industrial Integration Precision Medicine;Dept of Tangshan Key laboratory of Medical-Industrial Integration Precision Medicine;Clinical Medicine School,North China University of Science and Technology,Tangshan Hebei 063000,China;School of Pharmacy,North China University of Science and Technology,Tangshan Hebei 063210,China)

机构地区：[1]华北理工大学公共卫生学院,河北唐山063210 [2]华北理工大学附属医院放化疗科 [3]河北省医工融合精准医疗重点实验室 [4]唐山市医工融合精准医疗重点实验室 [5]华北理工大学临床医学院,河北唐山063000 [6]华北理工大学药学院,河北唐山063210

出　　处：《中国药理学通报》2025年第5期888-898,共11页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上项目(No 82472636);河北省创新能力提升计划项目(No 235A2403D);华北理工大学公共卫生学院高水平科研创新团队建设计划(No KYTD202309)。

摘　　要：目的探讨circ_0071653靶向miR-197-3p对食管鳞癌(esophageal squamous cell carcinoma,ESCC)细胞增殖和转移的影响。方法Sanger测序和核糖核酸外切酶耐受实验证实circ_0071653的环状结构。实时荧光定量聚合酶链反应(RT-qPCR)和组织荧光原位杂交实验检测circ_0071653的表达并分析其临床相关性。细胞荧光原位杂交和核质分离实验验证circ_0071653和miR-197-3p的亚细胞定位。生物信息学分析、双荧光素酶报告基因和RT-qPCR实验验证circ_0071653和miR-197-3p的相互作用。此外,CCK-8、集落形成、划痕、Transwell侵袭以及裸鼠皮下成瘤实验评估circ_0071653和miR-197-3p对细胞活性、增殖、迁移、侵袭以及体内成瘤能力的影响。结果circ_0071653为环状RNA,在ESCC细胞和癌组织中高表达,与ESCC患者的淋巴结转移和临床分期相关。circ_0071653和miR-197-3p均主要定位在细胞质,数据库预测显示circ_0071653与miR-197-3p存在互补结合位点,双荧光素酶和RT-qPCR实验证实二者结合。此外,敲低circ_0071653可抑制ESCC细胞的活性、增殖、迁移、侵袭以及裸鼠皮下成瘤能力,而下调miR-197-3p的表达可逆转该作用。结论circ_0071653通过靶向miR-197-3p促进ESCC恶性进展。Aim To investigate the effects of circ_0071653 targeting miR-197-3p on the proliferation and metastasis of esophageal squamous cell carcinoma(ESCC)cells.Methods The circular structure of circ_0071653 was confirmed by Sanger sequencing and ribonuclease R tolerance experiments.Real-time quantitative polymerase chain reaction(RT-qPCR)and tissue fluorescence in situ hybridization assay were performed to detect the circ_0071653 expression levels and analyze its clinical relevance.Cell fluorescence in situ hybridization and nuclear cytoplasmic separation assays were used to verify the subcellular localization of circ_0071653 and miR-197-3p.Bioinformatics analysis,dual luciferase reporter gene and RT-qPCR assays were conducted to validate the interactions between circ_0071653 and miR-197-3p.Moreover,the cell counting Kit-8(CCK-8),colony formation,scratch,Transwell invasion and subcutaneous tumor formation in nude mice assays were used to evaluate the effects of circ_0071653 and miR-197-3p on cell viability,proliferation,migration,and invasion and in vivo tumorigenesisability.Results Circ_0071653 was a circular RNA,which showed high expression in ESCC cell lines and tissues.The expression of circ_0071653 was significantly correlated with lymph node metastasis and clinical stage of ESCC patients.Circ_0071653 and miR-197-3p were mainly localized in the cytoplasm.The databases predict that circ_0071653 had complementary binding sites with miR-197-3p,and their binding were confirmed by dual luciferase reporter geneand RT-qPCR assays.Moreover,the activity,proliferation,migration,invasion and in vivo tumorigenesis abilities of ESCC cells were significantly reduced after knocking down circ_0071653,and this effect could be reversed by downregulating the expression of miR-197-3p.Conclusions Circ_0071653 promotes the malignant progression of ESCC through targeted regulation of miR-197-3p.

关 键 词：食管鳞状细胞癌 circ_0071653 miR-197-3p 增殖 迁移 侵袭 

分 类 号：R329.25[医药卫生—人体解剖和组织胚胎学] R329.28[医药卫生—基础医学] R342.2R735.1