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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。

Circ_0007429/miR-637/TRIM71/Ago2 axis participates in the regulation of proliferation, migration, invasion, apoptosis, and aerobic glycolysis of HCC.

机构信息

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Hubei Clinical Center & Key Laboratory of Intestinal & Colorectal Diseases, Wuhan, China.

出版信息

Mol Carcinog. 2023 Jun;62(6):820-832. doi: 10.1002/mc.23526. Epub 2023 Mar 15.

Abstract

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.

摘要

circRNAs 在肝细胞癌(HCC)的进展中发挥着重要作用,然而,circ_0007429 在 HCC 中的作用尚不清楚。我们使用生物信息学工具,选择在 HCC 组织中表达水平最高的 circ_0007429,并研究其在 HCC 进展中的作用。免疫组织化学、质粒转染、实时定量 PCR 和 Western blot 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 信号通路的调节作用及其在 HCC 进展中的关键作用。裸鼠异种移植模型用于体内检测肿瘤生长。与对照组相比,circ_0007429 和 TRIM71 的表达在 HCC 组织和细胞中上调,而 miR-637 的表达下调。circ_0007429 的敲低增强了 HCC 细胞的凋亡,而抑制了增殖、迁移、侵袭和有氧糖酵解,这些作用被 miR-637 抑制剂逆转。高水平的 circ_0007429 与 HCC 患者的生存率较差相关。此外,circ_0007429 干扰抑制了体内肿瘤的生长。TRIM71 直接与 miR-637 结合并抑制 Ago2 的表达。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,同时通过 miR/TRIM71/Ago2 轴抑制细胞凋亡,促进 HCC 的进展。这些结果为 HCC 的发病机制提供了分子见解,并表明 circ_0007429 可能成为 HCC 的治疗靶点。

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