Circ_0001955 Acts as a miR-646 Sponge to Promote the Proliferation, Metastasis and Angiogenesis of Hepatocellular Carcinoma

Background: Circular RNA (circRNA) exerts a crucial role in the progression of many cancers, including hepatocellular carcinoma (HCC). However, the function of circ_0001955 in HCC progression has been poorly studied.

Aims: Elucidating the role and molecular mechanism of circ_0001955 in HCC progression.

Methods: Quantitative real-time PCR was employed to detect the expression of circ_0001955 and miR-646. Cell counting kit 8 assay, Ethynyl-2-deoxyuridine assay, flow cytometry, transwell assay, and tube formation assay were conducted to measure cell proliferation, metastasis, angiogenesis and apoptosis. Dual-luciferase reporter assay and biotin-labeled RNA pull-down assay were performed to analyze the interactions among circ_0001955, miR-646 and frizzled class receptor 4 (FZD4). Moreover, animal experiments were performed to examine the influence of circ_0001955 on HCC tumor growth in vivo.

Results: Circ_0001955 was a highly expressed circRNA in HCC tissues and cells. Circ_0001955 knockdown inhibited the proliferation, metastasis, angiogenesis, and enhanced the apoptosis of HCC cells. Meanwhile, miR-646 could be sponged by circ_0001955, and its inhibitor could reverse the negative regulation of circ_0001955 knockdown on HCC progression. Further, FZD4 was a target of miR-646, and its overexpression could invert the inhibition effect of miR-646 mimic on HCC progression. Besides, our results also indicated that circ_0001955 promoted FZD4 expression by sponging miR-646. Animal experiment results showed that circ_0001955 silencing restrained HCC tumor growth in vivo.

Conclusion: Our findings suggested that circ_0001955 might play a positive role in HCC progression via regulating the miR-646/FZD4 axis, indicating that circ_0001955 might be a potential therapeutic target for HCC.