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Circ_0007429/miR-637/TRIM71/Ago2 axis participates in the regulation of proliferation, migration, invasion, apoptosis, and aerobic glycolysis of HCC
Molecular Carcinogenesis ( IF 3.0 ) Pub Date : 2023-03-15 , DOI: 10.1002/mc.23526
Lilan Fan 1, 2 , Panpan Xia 1, 2 , Jing Wang 1, 2 , Shun Xu 1, 2 , Zijian Qiu 1, 2 , Yan Wu 1, 2 , Maohui Feng 3, 4, 5 , Qiu Zhao 1, 2 , Hongling Wang 1, 2 , Xuanfei Li 3, 4, 5
Affiliation  

CircRNAs play an important role in the progression of hepatocellular carcinoma (HCC), however, the role of circ_0007429 in HCC remains unknown. Using bioinformatics tools, we selected circ_0007429 that was most highly expressed in HCC tissues and investigated its role in HCC progression. Immunohistochemistry, plasmid transfection, real-time quantitative PCR, and western blot analysis were used to identify the relationship between circ_0007429 and its potential target, miR-637, and TRIM71. The regulatory effect of circ_0007429 on miR-637/TRIM71/Ago2 signaling and its key role in HCC progression were studied in vitro. A nude mouse xenograft model was used to examine tumor growth in vivo. Circ_0007429 and TRIM71 expression were upregulated, while miR-637 expression was downregulated in HCC tissues and cells compared with their expression in control groups. Knockdown of circ_0007429 enhanced apoptosis in HCC cells, while impeded proliferation, migration, invasion, and aerobic glycolysis, which were reversed by miR-637 inhibitor. High levels of circ_0007429 correlated with a poor survival rate of HCC patients. Additionally, circ_0007429 interfering inhibited tumor growth in vivo. TRIM71 directly bound to miR-637 and inhibited Ago2 expression. Moreover, circ_0007429 promotes aerobic glycolysis in HCC cells through the miR/TRIM71/Ago2 axis. Circ_0007429 promotes HCC progression by promoting cell proliferation, migration, invasion, and aerobic glycolysis and by inhibiting cell apoptosis through the miR/TRIM71/Ago2 axis. These results provide molecular insights into the mechanism of HCC and suggest that circ_0007429 could be a therapeutic target for HCC.

中文翻译:

Circ_0007429/miR-637/TRIM71/Ago2轴参与调控HCC的增殖、迁移、侵袭、凋亡和有氧糖酵解

circRNA 在肝细胞癌(HCC)的进展中起着重要作用,然而,circ_0007429 在 HCC 中的作用仍然未知。使用生物信息学工具,我们选择了在 HCC 组织中表达最高的 circ_0007429 并研究了它在 HCC 进展中的作用。免疫组织化学、质粒转染、实时定量 PCR 和蛋白质印迹分析用于鉴定 circ_0007429 与其潜在靶标 miR-637 和 TRIM71 之间的关系。在体外研究了 circ_0007429 对 miR-637/TRIM71/Ago2 信号的调节作用及其在 HCC 进展中的关键作用。使用裸鼠异种移植模型来检查体内肿瘤生长。Circ_0007429 和 TRIM71 表达上调,而miR-637在HCC组织和细胞中的表达较对照组明显下调。敲低 circ_0007429 可增强 HCC 细胞的凋亡,同时阻碍增殖、迁移、侵袭和有氧糖酵解,这些可被 miR-637 抑制剂逆转。高水平的 circ_0007429 与 HCC 患者的低存活率相关。此外,circ_0007429 干扰抑制体内肿瘤生长。TRIM71 直接结合 miR-637 并抑制 Ago2 表达。此外,circ_0007429 通过 miR/TRIM71/Ago2 轴促进 HCC 细胞的有氧糖酵解。Circ_0007429 通过促进细胞增殖、迁移、侵袭和有氧糖酵解以及通过 miR/TRIM71/Ago2 轴抑制细胞凋亡来促进 HCC 进展。
更新日期:2023-03-15
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