MicroRNA-1468-5p inhibits glioma cell proliferation and induces cell cycle arrest by targeting RRM1.

MicroRNAs are associated with different types of cancers. In this study, we found that miR-1468-5p could inhibit growth and cell cycle progression in glioma by targeting ribonucleotide reductase large subunit M1 (RRM1). First, we analyzed miR-1468-5p expression in different glioma grades and the prognostic significance of its expression in glioblastoma multiform patients from the Chinese Glioma Genome Atlas. Then, we expressed miR-1468-5p in U87 and U251 cells and assessed the effects on proliferation and cell cycle progression using cell counting kit-8, colony formation, EdU and flow cytometry assays. Western blotting and luciferase reporter assays identified RRM1 as a novel direct target of miR-1468-5p. Experiments to determine the role of RRM1 in glioma showed that RRM1 expression was significantly higher in glioma than in normal brain tissues, and silencing RRM1 with small-interfering RNAs decreased proliferation and suppressed cell cycle progression, which indicated that RRM1 had pro-tumor functions. miR-1468-5p overexpression suppressed RRM1 expression, reduced glioma cell proliferation and induced cell cycle arrest, which was partially rescued by forced RRM1 expression. In summary, our study revealed that the regulatory mechanism of miR-1468-5p in glioma cell cycle progression involved direct regulation of RRM1 expression, suggesting that RRM1 may be a potential therapeutic target for glioma.