LncRNA MIR4435‐2HG potentiates the proliferation and invasion of glioblastoma cells via modulating miR‐1224‐5p/TGFBR2 axis. Issue 11 (22nd April 2020) - Xu, Hongchao
Abstract: Glioblastoma (GBM) belongs to the high‐grade (IV) gliomas with extremely poor prognosis. Accumulating evidence uncovered the key roles of long non‐coding RNAs (lncRNAs) in GBM development. This study aimed to determine the biological actions and the clinical relevance of lncRNA MIR4435‐2 Host Gene (MIR4435‐2HG) in GBM. Data from GEPIA database showed that MIR4435‐2HG was up‐regulated in GBM tissues and high expression of MIR4435‐2HG correlated with shorter overall survival of GBM patients. Further experimental assays verified the up‐regulation of MIR4435‐2HG in GBM tissues and cell lines. In vitro cell studies and in vivo animal studies showed that knockdown of MIR4435‐2HG resulted in the inhibition of GBM cell proliferation and invasion and in vivo tumour growth, while MIR4435‐2HG overexpression driven GBM progression. Furthermore, MIR44435‐2HG was found to sponge miR‐1224‐5p and suppress miR‐1224‐5p expression; overexpression of miR‐1224‐5p attenuated the enhancement in GBM cell proliferation and invasion induced by MIR4435‐2HG overexpression. In a subsequent study, miR‐1224‐5p was found to target transforming growth factor‐beta receptor type 2 (TGFBR2) and repressed TGFBR2 expression, and in vitro assays showed that miR‐1224‐5p exerted tumour‐suppressive effects via targeting TGFBR2. More importantly, TGFRB2 knockdown antagonized hyper‐proliferation and invasion of GBM cells with MIR4435‐2HG overexpression. Clinically, the down‐regulation of miR‐1224‐5p and up‐regulation of TGFBR2 were verified in the GBM clinical samples. Taken together, the present study suggests the oncogenic role of MIR4435‐2HG in GBM and underlies the key function of MIR4435‐2HG‐driven GBM progression via targeting miR‐1224‐5p/TGFBR2 axis.