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

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

Integrated analysis of histone lysine lactylation (Kla)-specific genes suggests that NR6A1, OSBP2 and UNC119B are novel therapeutic targets for hepatocellular carcinoma

“…Moreover, lactic acid accumulation inhibits the immune process 21 , and leads to tumor immune escape via impairing tumor surveillance by T or NK cells 11 . Remodeling glycolysis is a common phenomenon in HCC, which is associated with HCC progression 22 , lenvatinib 23 and chemoresistance 24 . Lactic acid accumulates in HCC TME during aerobic glycolysis, and histone Kla is sensitive to lactate level.…”

Biological functions of circRNA in regulating the hallmarks of gastrointestinal cancer (Review)

“…circ-0007429 is aberrantly upregulated in HCC tissues and is positively correlated with poor clinical outcomes. circ-0007429 acts as a sponge targeting the tumor suppressor, miR-637, to promote TRIM71 expression and affect the expression of its downstream molecule, argonaute-2, which promotes HCC progression and aerobic glycolysis in vitro and in vivo (94). Downregulation of circRNAs in HCC.…”