Hsa_circ_0000418 promotes the progression of glioma by regulating microRNA-409-3p / pyruvate dehydrogenase kinase 1 axis

Abstract

ABSTRACT Glioma is the commonest intracranial malignancy, and circRNAs are important regulatory factors which are implicated in the development of glioma. Nonetheless, the role of circRNAs in glioma is largely unknown. The research is performed to elaborate on the biological role of has_circ_0000418 (circ_0000418) in glioma progression and its potential molecular mechanism. The differentially expressed circRNAs in glioblastoma patient derived cells and neural progenitor cells were analyzed based on the microarray data of GSE146463. Additionally, qRT-PCR and Western blot experiments were conducted to measure the expression of circ_0000418, microRNA-409-3p (miR-409-3p) and pyruvate dehydrogenase kinase 1 (PDK1) in glioma tissues/cells. Cell growth and cell cycle distribution were monitored using CCK-8 assay, BrdU assay and flow cytometry. Bioinformatics prediction, dual-luciferase reporter gene experiment and RIP assay were conducted to verify the targeting relationship between circ_0000418 and miR-409-3p, miR-409-3p and PDK1 3ʹUTR. In this work, we observed that, circ_0000418 expression level was significantly up-regulated in glioma tissues and cell lines. Circ_0000418 overexpression facilitated glioma cell growth and accelerated cell cycle progression, while knockdown of circ_0000418 produced the opposite effects. Circ_0000418 specifically combined with miR-409-3p, and circ_0000418 negatively modulated the expression of miR-409-3p. PDK1 acted as a target gene of miR-409-3p, and PDK1 could be positively and indirectly modulated by circ_0000418 in glioma cells. In summary, circ_0000418 enhances glioma cell growth and accelerates cell cycle progression by regulating miR-409-3p/PDK1 axis.