miR-30 overexpression promotes glioma stem cells by regulating Jak/STAT3 signaling pathway

Abstract

Malignant glioma is the most common intracranial tumor with poor prognosis. It is well believed that glioma stem cells (GSCs) are responsible for the initiation and progression of glioma. Janus kinase/signal transducer and activator of transcription (Jak/STAT3) pathway plays a key role in the functions of GSCs. However, the regulatory mechanism of Jak/STAT3 pathway has not been completely elucidated. This study employed multidisciplinary approaches to investigate the upstream regulators of Jak/STAT3 signaling in GSCs. miR-30 was found to be overexpressed in the GSCs derived from U-87 MG and primary glioma cells, compared with non-stem-cell-like glioma cells and normal cells. Downregulation of miR-30 was able to suppress Jak/STAT3 pathway and reduce the tumorigenecity of GSCs. miR-30 decreased the expression of suppressor of cytokine signaling 3 (SOCS3) expression by targeting 3′UTR of its mRNA. The silencing of SOCS3 abolished the effect of miR-30 downregulation on GSCs. Collectively, there is a regulatory pathway consisting of miR-30, SOCS3, and Jak/STAT3 in GSCs, and targeting this pathway may be a promising strategy to treat glioma.