Zhang Jia Wei, Wang Xing, Li Gao Chao, Wang Dong, Han Sheng, Zhang Yao Dong, Luo Chen Huan, Wang Hong Wei, Jiang Wang Jie, Li Chang Xian, Li Xiang Cheng
Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, Nanjing, Jiangsu Province, China.
J Cancer. 2020 Mar 26;11(12):3604-3614. doi: 10.7150/jca.41437. eCollection 2020.
: MicroRNAs (miRNAs) play important roles in the occurrence and development of cancers. In this project, we aimed to explore the role and molecular mechanism of mir-30a-5p in cholangiocarcinoma (CCA). : The expression profile and clinical significance of miR-30a-5p in CCA patients were investigated in 31 ICC and 52 ECC patients respectively. The role and mechanism of miR-30a-5p in CCA cells were investigated by up-regulating and inhibiting miR-30a-5p expression functional study. : The expression of miR-30a-5p was increased in both CCA tissues and cells. The inhibition of miR-30a-5p decreased cell proliferation and induced cell apoptosis while overexpression of miR-30a-5p achieved the opposite effect. Furthermore, SOCS3 was down-regulated in ICC and ECC tissues and negatively regulated by miR-30a-5p. Dual-luciferase reporter assay revealed that co-transfection of miR-30a-5p significantly inhibited the activity of firefly luciferase reporter carrying the wild-type 3'UTR of SOCS3. The inhibition of SOCS3 could largely rescue the inhibitory effect of miR-30a-5p inhibition on CCA cells proliferation. In clinical, up-regulated miR-30a-5p expression was correlated with large tumor size in both ICC and ECC cohorts. : miR-30a-5p promoted CCA cells proliferation through targeting SOCS3. These findings suggested that miR-30a-5p could be a potential therapeutic target.
微小RNA(miRNA)在癌症的发生和发展中起重要作用。在本项目中,我们旨在探讨mir-30a-5p在胆管癌(CCA)中的作用及分子机制。分别在31例肝内胆管癌(ICC)患者和52例肝外胆管癌(ECC)患者中研究了miR-30a-5p在CCA患者中的表达谱及临床意义。通过上调和抑制miR-30a-5p表达的功能研究,探讨了miR-30a-5p在CCA细胞中的作用及机制。miR-30a-5p在CCA组织和细胞中均表达增加。抑制miR-30a-5p可降低细胞增殖并诱导细胞凋亡,而miR-30a-5p过表达则产生相反的效果。此外,细胞因子信号转导抑制因子3(SOCS3)在ICC和ECC组织中表达下调,并受miR-30a-5p负调控。双荧光素酶报告基因检测显示,共转染miR-30a-5p可显著抑制携带SOCS3野生型3'非翻译区(3'UTR)的萤火虫荧光素酶报告基因的活性。抑制SOCS3可在很大程度上挽救miR-30a-5p抑制对CCA细胞增殖的抑制作用。在临床上,miR-30a-5p表达上调与ICC和ECC队列中的肿瘤大尺寸相关。miR-30a-5p通过靶向SOCS3促进CCA细胞增殖。这些发现表明miR-30a-5p可能是一个潜在的治疗靶点。