Steroid receptor coactivator‐1 enhances the stemness of glioblastoma by activating long noncoding RNA XIST/miR‐152/KLF4 pathway

Glioblastoma (GBM) recurrence is attributed to the presence of therapy‐resistant glioblastoma stem cells. 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 investigate the role of SRC‐1 in GBM. In this study, we found that SRC‐1 expression is positively correlated with grades of glioma and inversely correlated with glioma patient’s prognosis. Steroid receptor coactivator‐1 promotes the proliferation, migration, and tumor growth of GBM cells. Notably, SRC‐1 knockdown suppresses the stemness of GBM cells. Mechanistically, long noncoding RNA X‐inactive specific transcript (XIST) is regulated by SRC‐1 at the posttranscriptional level and mediates the function of SRC‐1 in promoting stemness‐like properties of GBM. Steroid receptor coactivator‐1 can promote the expression of Kruppel‐like factor 4 (KLF4) through the XIST/microRNA (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 the long noncoding RNA XIST/miR‐152/KLF4 pathway and provides novel markers for diagnosis and therapy of GBM.