Reduced PTEN expression and overexpression of miR-17-5p, -19a-3p, -19b-3p, -21-5p, -130b-3p, -221-3p and -222-3p by glioblastoma stem-like cells following irradiation

Abstract

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene that induces cell apoptosis by inhibiting the PI3K/Akt signaling pathway. Glioblastoma (GBM) is a brain tumor that is resistant to irradiation and chemotherapy and, thus, is difficult to cure. GBM stem-like cells (GSCs) have been implicated as a cause of this resistance. microRNA (miRNA/miR) inhibits the expression of proteins. The objective of the present study was to identify miRNAs that target PTEN, which induces apoptosis, in irradiation-resistant GSCs. When the expression of miRNAs was examined in GSCs irradiated at 60 Gy using the human GBM A172 cell line, the expression of PTEN-targeting miR-17-5p, -19a-3p, -19b-3p, -21-5p, -130b-3p, -221-3p and -222-3p was significantly higher in irradiated GSCs than in non-irradiated cells, and the PTEN expression levels, as revealed by immunostaining, were lower in the irradiated GSCs than in the non-irradiated cells. These results suggested that the expression of PTEN was suppressed through the overexpression of PTEN-targeting miRNAs in GSCs following irradiation.