4.7 Article

Circ_0000854 regulates the progression of hepatocellular carcinoma through miR-1294/IRGQ axis

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CLINICAL IMMUNOLOGY
卷 238, 期 -, 页码 -

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ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2022.109007

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Circ_0000854; miR-1294; IRGQ; Hepatocellular carcinoma

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This study found that circ_0000854 promotes the progression of HCC through the miR-1294/IRGQ axis, providing a novel regulatory mechanism for HCC pathogenesis.
Background: Hepatocellular carcinoma (HCC) is a common cancer disease with the second highest mortality. Circular RNAs (circRNAs) have been shown to play key roles in many tumors, including HCC. However, the function of circ_0000854 in the progression of HCC has not been clarified. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of circ_0000854, microRNA-1294 (miR-1294) and immunity related GTPase Q (IRGQ) in HCC cells and tissues. Western blot was used for protein expression analysis. Cell processes were detected by 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium Bromide (MTT) assay, thymidine analog 5-ethynyl-2'-deoxyuridine (EdU) assay, transwell assay, flow cytometry, and wound healing assay. Mechanically, the interaction of miR-1294 with circ_0000854 or IRGQ was notarized by dual-luciferase reporter assay and RNA pull-down assay. The xenotransplantation model was established to study the role of circ_0000854 in vivo. Results: Circ_0000854 and IRGQ were highly expressed in HCC tissues and cells, while miR-1294 was down regulated. Silencing circ_0000854 suppressed HCC cell malignant behaviors, including proliferation, cell cycle progression, migration and invasion. Circ_0000854 exhibited sponge effect on miR-1294 and miR-1294 inhibition reversed function of circ_0000854 knockdown. In addition, miR-1294 targeted IRGQ and circ_0000854 sponged miR-1294 to upregulate IRGQ. Overexpression of IRGQ restored miR-1294-induced anti-tumor regulation in HCC cells. Animal experiments confirmed that silencing circ_0000854 inhibited tumor growth and metastasis of HCC via mediating miR-1294 and IRGQ levels in vivo. Conclusion: Circ_0000854 accelerated HCC progression via the miR-1294/IRGQ axis, providing a novel regulatory mechanism for HCC pathogenesis.

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