LncRNA SNHG11 Promotes Temozolomide Resistance in Glioblastoma via Promoting MGMT Expression
Abstract Background Acquired TMZ resistance is considered as the main reason for the poor prognosis of glioblastoma (GBM) patients. However, underlying mechanism remains unknown. Long noncoding RNAs (lncRNAs) have emerged as important regulators in multiple biological processes. Methods SNHG11 expression in cells and GBM tissues was measured using qRT-PCR. In vitro studies, including CCK-8, colony formation assay, flow cytometry and western blot, were employed to measure the role of SNHG11. Interaction between miR-7-5p, SNHG11, and IRS2 was examined by dual luciferase reporter assay, as well as RNA binding protein immunoprecipitation (RIP) assay. CHIP assays were used to measure the role of SNHG11/miR-7-5p/IRS2 axis on modulating the H3K9 acetylation of MGMT. Results SNHG11 overexpression in GBM tissues contributes to TMZ resistance. In vitro and in vivo studies confirmed that SNHG11 promoted TMZ resistance in GBM cells. In addition, SNHG11 conferred TMZ resistance through increasing MGMT expression. Furthermore, SNHG11 could function as ceRNA by sponging miR-7-5p, which led to increased IRS2 expression. SNHG11/miR-7-5p/IRS2 axis increased MGMT expression by promoting the acetylation of H3K9 in MGMT promoter regions. Conclusion Taken together, our results revealed that targeting SNHG11 is a potential therapy to overcome TMZ resistance. And SNHG11 in GBM tissues is a potential biomarker for predicting response to TMZ.