SRC-1 enhances the stemness of glioblastoma by activating lncRNA XIST/ miR-152/ KLF4 pathway.

Glioblastoma (GBM) recurrence is attributed to the presence of therapy-resistant glioblastoma stem cells (GSCs). Steroid receptor coactivator-1 (SRC-1) acts as an oncogenic regulator in many human tumors. The relationship between SRC-1 and GBM has not yet been studied. Herein, we would like to investigate the role of SRC-1 in GBM. In this study, we demonstrated that SRC-1 expression is positively correlated with grades of glioma and inversely correlated with glioma patient's prognosis. SRC-1 promotes the proliferation, migration and tumor growth of GBM cells. Notably, SRC-1 knockdown suppresses the stemness of GBM cells. Mechanistically, lncRNA X-inactive specific transcript (XIST) is regulated by SRC-1 at the post-transcriptional level and mediate the function of SRC-1 in promoting stemness-like properties of GBM. SRC-1 can promote the expression of KLF4 through the XIST/miR-152 axis. Additionally, arenobufagin and bufalin, SRC small molecule inhibitors, can reduce the proliferation and stemness of GBM cells. This study reveals SRC-1 promotes the stemness of GBM by activating lncRNA XIST/ miR-152/ KLF4 pathway and provides novel markers for diagnosis and therapy of GBM.