Knockdown of long non-coding RNA ANRIL inhibits proliferation, migration, and invasion but promotes apoptosis of human glioma cells by upregulation of miR-34a.

ABSTRACT

Gliomas are the most common types of primary central nervous system malignancy found in adults. Long non-coding RNA antisense non-coding RNA in the INK4 locus (ANRIL) variants are associated with glioma and miR-34a is markedly downregulated in U251 glioma cells. The 3'-untranslated region (3'UTR) of silent information regulator 1 (Sirt1) contains a conserved site that is targeted directly by miR-34a. Therefore, in this study, we investigated the roles of ANRIL, miR-34a, and Sirt1 in glioma and their potential interactions. Firstly, expression of ANRIL in normal glia cells and five glioma cell lines was measured. Then, effects of ANRIL suppression on cell proliferation, apoptosis, migration and invasion of U251 cells as well as expression of miR-34a were assessed. Meanwhile, effects of miR-34a on U251 cells silencing ANRIL were tested. Whether Sirt1 is a target of miR-34a was verified, followed by estimating the role of Sirt1 overexpression in U251 cells overexpressing miR-34a. Finally, the involved signaling pathways were assessed. ANRIL was upregulated in glioma cells and its suppression inhibited cell proliferation, migration and invasion but promoted cell apoptosis. ANRIL acted as a sponge of miR-34a, and Sirt1 is a target of miR-34a. Then, Sirt1 was proved to function through activation of the PI3K/AKT and mTOR signaling pathways. In conclusion, ANRIL was upregulated in glioma, and its inhibition could repress cell proliferation, migration and invasion but inhibit cell apoptosis through miR-34a-mediated downregulation of Sirt1, involving the inactivation of the PI3K/AKT and mTOR pathways.