人源环状RNA hsa_circ_0007059通过PTEN-AKT/mTOR信号通路吸附miR-421，从而抑制肝癌细胞的生长和干性。
Hsa_circ_0007059 sponges miR-421 to repress cell growth and stemness in hepatocellular carcinoma by the PTEN-AKT/mTOR pathway.
作者信息
Hui Yongfeng, Jin Dong, Leng Junzhi, Liu Di, Yuan Peng, Tang Chaofeng, Wang Qi
机构信息
Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, PR China.
Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, PR China.
出版信息
Pathol Res Pract. 2022 Jan;229:153692. doi: 10.1016/j.prp.2021.153692. Epub 2021 Nov 19.
BACKGROUND
Hepatocellular carcinoma (HCC) is a substantial health concern worldwide. Increasing studies have suggested that circle RNAs (circRNAs) function as new regulators in HCC progression. The present work explored the role of hsa_circ_0007059 (circ_0007059) in the developing process of hepatocarcinogenesis.
METHODS
The circ_0007059 level in HCC was determined by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and northern blot. Its biological role in HCC cells was assessed using 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry, Transwell, sphere formation and western blotting analyses. Bioinformatics analysis, luciferase reporter, and RNA immunoprecipitation (RIP) assays were used to test the regulatory mechanisms of circ_0007059.
RESULTS
Our results revealed that circ_0007059 expression was downregulated in HCC samples and cells. Moreover, circ_0007059 overexpression inhibited HCC cell proliferation, migration, invasion, and stem cell-like property, and strengthened cell apoptosis. In mechanism, circ_0007059 suppressed AKT/mTOR pathway by positively regulating phosphatase and tensin homolog (PTEN) expression. Additionally, circ_0007059 acted as a positive regulator of PTEN through controlling the availability of miR-421. Rescue assays demonstrated that PTEN knockdown or SC79 (AKT agonist) eliminated the effect of circ_0007059 on HCC cell phenotypes.
CONCLUSION
Circ_0007059 sponges miR-421 to inhibit oncogenic cellular process in HCC by mediating the PTEN-AKT/mTOR pathway.
背景
肝细胞癌（HCC）是全球范围内严重的健康问题。越来越多的研究表明，环状RNA（circRNAs）在肝癌进展中作为新的调节因子发挥作用。本研究探讨了hsa_circ_0007059（circ_0007059）在肝癌发生发展过程中的作用。
方法
通过逆转录定量聚合酶链反应（RT-qPCR）和Northern印迹法测定HCC中circ_0007059的水平。使用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）、集落形成、流式细胞术、Transwell、球体形成和蛋白质印迹分析评估其在HCC细胞中的生物学作用。采用生物信息学分析、荧光素酶报告基因和RNA免疫沉淀（RIP）实验来检测circ_0007059的调控机制。
结果
我们的结果显示，circ_0007059在HCC样本和细胞中的表达下调。此外，circ_0007059过表达抑制HCC细胞增殖、迁移、侵袭和干细胞样特性，并增强细胞凋亡。机制上，circ_0007059通过正向调节磷酸酶和张力蛋白同源物（PTEN）的表达来抑制AKT/mTOR通路。此外，circ_0007059通过控制miR-421的可用性来作为PTEN的正向调节因子。挽救实验表明，PTEN敲低或SC79（AKT激动剂）消除了circ_0007059对HCC细胞表型的影响。
结论
Circ_0007059通过介导PTEN-AKT/mTOR通路海绵化miR-421以抑制HCC中的致癌细胞过程。
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