Circ_0000284 Facilitates the Growth, Metastasis and Glycolysis of Intrahepatic Cholangiocarcinoma Through MiR-152-3p-mediated PDK1 Expression

Background: Circular RNAs (circRNAs) are key molecules in the regulation of intrahepatic cholangiocarcinoma (ICC) progression. The purpose of this study was to analyze the function and underlying molecular mechanism of circ_0000284 in ICC.

Methods: Quantitative real-time PCR was used to analyze the circ_0000284, microRNA (miR)-152-3p and pyruvate dehydrogenase kinase 1 (PDK1) expression. Cell proliferation, apoptosis, invasion and migration were executed by cell counting kit 8 assay, EdU assay, flow cytometry, transwell assay and wound healing assay, respectively. All protein expression levels were examined using western blot analysis. Cell glycolysis was analyzed by detecting glucose consumption, lactate production and ATP/ADP ratios. Target relationship was estimated by dual-luciferase reporter assay. The effect of circ_0000284 on ICC tumor growth in vivo was evaluated by constructing xenograft mice model.

Results: We detected high expression of circ_0000284 in ICC tumor tissues and cells. Downregulated circ_0000284 inhibited ICC cell proliferation, invasion, migration, glycolysis, and accelerated apoptosis. MiR-152-3p was sponged by circ_0000284, and its inhibitor revoked the effect of circ_0000284 knockdown on ICC cell progression. PDK1 was a target of miR-152-3p, and its expression was suppressed by circ_0000284 knockdown. PDK1 overexpression reversed the inhibition effect of miR-152-3p on ICC cell growth, metastasis and glycolysis. In animal experiments, circ_0000284 downregulation also inhibited ICC tumor growth.

Conclusion: Circ_0000284 promoted the growth, metastasis and glycolysis of ICC by miR-152-3p/PDK1 pathway, showing that circ_0000284 was a potential therapeutic target for ICC.