CircYIPF6 regulates glioma cell proliferation, apoptosis, and glycolysis through targeting miR-760 to modulate PTBP1 expression

Transl Neurosci. 2023 Aug 11;14(1):20220271. doi: 10.1515/tnsci-2022-0271. eCollection 2023 Jan 1.

Abstract

Background: Recent studies have highlighted that circular RNAs regulate cancer-related genes' expression by functioning as microRNA sponges in cancers. Herein, we investigated the function and molecular mechanism of circYIPF6 in glioma.

Methods: 5-Ethynyl-2'-deoxyuridine assay, colony formation, and flow cytometry were performed to assess the proliferation and apoptosis of glioma cells. The levels of glycolytic metabolism were evaluated by measuring the glucose uptake and lactate production. The protein levels of Bax, Bcl2, GLUT1, LDHA, and PTBP1 were examined by western blot. The interplay between miR-760 and circYIPF6 or PTBP1 was confirmed by a dual-luciferase reporter. The effect of circYIPF6 silencing on the growth of glioma in vivo was determined by a xenograft experiment.

Results: circYIPF6 was significantly upregulated in glioma. Knockdown of circYIPF6 suppressed glioma cell proliferation and glycolysis while promoting cell apoptosis. Mechanistic studies revealed that circYIPF6 targeted miR-760 and could abundantly sponge miR-760 to inhibit the expression of its downstream target gene PTBP1. Functional rescue experiments showed that both miR-760 inhibition and PTBP1 overexpression could attenuate the regulatory effect of circYIPF6 silencing on glioma cells. Furthermore, circYIPF6 knocking down effectively impeded glioma growth in vivo.

Conclusion: These findings suggested that circYIPF6 participated in the proliferation, apoptosis, and glycolysis of glioma through the miR-760/PTBP1 axis.

Keywords: PTBP1; apoptosis; circYIPF6; glioma; glycolysis; miR-760; proliferation.