miR-519a enhances chemosensitivity and promotes autophagy in glioblastoma by targeting STAT3/Bcl2 signaling pathway

• DOI: 10.1186/s13045-018-0618-0
• Publication Date: 2018-05-29T14:17:33Z
• Authors: Hong Li; Lei Chen; Jun-jie Li; Qiang Zhou; Annie Huang; Wei-wen Liu; Ke Wang; Liang Gao; Song-tao Qi; Yun-tao Lu
• Keywords: Hematology; Temozolomide; Pathway Analysis

Chemoresistance to temozolomide (TMZ) is a major challenge in the treatment of glioblastoma (GBM). We previously found that miR-519a functions as tumor suppressor glioma by targeting signal transducer and activator transcription 3 (STAT3)-mediated autophagy oncogenic pathway. Here, we investigated effects on TMZ chemosensitivity GBM cells. Furthermore, underlying molecular mechanisms signaling pathways were explored.In present study, two stable TMZ-resistant cell lines successfully generated exposure parental cells gradually increasing concentration. After transfecting U87-MG/TMZ U87-MG with mimic or inhibitor, series biochemical assays such MTT, apoptosis, colony formation performed determine chemosensitive response TMZ. The levels detected transmission electron microscopy, LC3B protein immunofluorescence, Western blotting analysis. Stable knockdown overexpression established using lentivirus. A xenograft nude mouse model situ brain used examine vivo miR-519a. Tumor tissue samples collected from 48 patients assess relationship between STAT3 expression.TMZ significantly upregulated but not Moreover, expression baseline was lower compared dramatically enhanced TMZ-induced apoptotic death cells, while inhibition promoted resistance reduced induced through modification expression. results showed can enhance apoptosis sensitized promoting STAT3/Bcl-2/Beclin-1 In human tissues, an inverse correlation expression.Our suggested increased sensitivity therapy. positive may be mediated autophagy. addition, induce inhibiting STAT3/Bcl-2 Therefore, combination represent effective therapeutic strategy GBM.