MiR‑767‑5p inhibits glioma proliferation and metastasis by targeting SUZ12.

Abstract

A growing body of evidence implicates aberrant expression of microRNAs (miRNAs) and dysregulation of mRNA translation in the development and growth of cancer cells. However, little is known about the mechanisms of action of miRNAs in glioma, the most common form of adult-onset malignant brain tumor. In the present study, the expression and function of miR-767-5p were examined in human glioblastoma multiforme (GBM) tissue specimens and cell lines. miR-767-5p expression levels were analyzed by quantitative reverse-transcription PCR; cell proliferation was assessed by CCK-8, colony formation and 5-ethynyl-2′-deoxyuridine (EDU) assays; the cell cycle phase and apoptosis were detected by flow cytometry; and cell invasiveness was analyzed using wound healing and Transwell invasion assays. It was revealed found that miR-767-5p was significantly upregulated in GBM tissues (n=18) compared with normal brain tissues (n=8) and in 6 GBM cell lines compared with normal human astrocytes. Ectopic expression of miR-767-5p suppressed proliferation, colony formation, and migration, and promoted cell cycle arrest and apoptosis in GBM cell lines in vitro, and inhibited GBM tumor growth in a mouse xenograft model. Bioinformatics analysis identified the PRC2 component suppressor of zeste-12 (SUZ12) as a putative target of miR-767-5p. Co-transfection of miR-767-5p inhibited the activity of a luciferase reporter construct driven by the wild-type 3′ untranslated region of SUZ12 mRNA, but this was abolished by mutation of the putative miR-767-5p-binding sites. Consistent with the possibility that miR-767-5p acts by regulating SUZ12 expression, it was revealed that the inhibitory effects of miR-767-5p on GBM cell phenotypes were reversed by overexpression of SUZ12. Our results indicated that forced upregulation of miR-767-5p may represent a novel therapeutic strategy for glioma patients by targeting SUZ12.