title: Growth-inhibitory and chemosensitizing effects of microRNA-31 in human glioblastoma multiforme cells.
abstract: The constitutive activation of signal transducer and activator of transcription 3 (STAT3) contributes to resistance to temozolomide (TMZ) in glioblastoma multiforme (GBM). The aim of this study was to explore the biological role of microRNA-31 (miR-31) in GBM, particularly its role in the regulation of TMZ chemosensitivity. For this purpose, the human GBM cell lines, U251 and U87, were transfected with a miR-31 precursor (pre-miR-31), and cell proliferation, apoptosis and STAT3 phosphorylation were then assessed. To evaluate the effects of miR-31 on TMZ cytotoxicity, the cells were transfected with pre-miR-31 and exposed to 100 µM TMZ for 72 h prior to cell proliferation and apoptosis analysis. A constitutively active STAT3 mutant was co-transfected with pre-miR-31 into the cells to confirm the mediating role of STAT3 signaling. The enforced expression of miR-31 significantly reduced cell proliferation and induced mitochondrial apoptosis, as manifested by the loss of mitochondrial membrane potential and the increase in caspase-9 and caspase-3 activity. The phosphorylation level of STAT3 was significantly decreased by the overexpression of miR-31. The co-delivery of the constitutively active STAT3 mutant blocked the tumor suppressive effects of miR-31. In addition, miR-31 overexpression significantly enhanced the cytotoxic effects of TMZ on the GBM cells, as evidenced by the accelerated suppression of cell proliferation and the induction of apoptosis. The chemosensitizing effects of miR-31 were significantly impaired by the expression of the constitutively active STAT3 mutant. Taken together, our results indicate that miR-31 triggers mitochondrial apoptosis and potentiates TMZ cytotoxicity in GBM cells largely through the suppression of STAT3 activation. Thus, the restoration of miR-31 expression may be of therapeutic beenefit in the treatment of GBM.
authors: Luqiao Hospital of Taizhou Enze Medical Center (Group), Taizhou, Zhejiang 318050, P.R. China.
authors: Rong-Jing
authors: RJ
authors: Zhou
authors: Luqiao Hospital of Taizhou Enze Medical Center (Group), Taizhou, Zhejiang 318050, P.R. China.
authors: Xiong-Ying
authors: XY
authors: Xu
authors: Luqiao Hospital of Taizhou Enze Medical Center (Group), Taizhou, Zhejiang 318050, P.R. China.
authors: Bu-Xing
authors: BX
authors: Liu
authors: Luqiao Hospital of Taizhou Enze Medical Center (Group), Taizhou, Zhejiang 318050, P.R. China.
authors: Wen-Zhen
authors: WZ
authors: Dai
authors: Luqiao Hospital of Taizhou Enze Medical Center (Group), Taizhou, Zhejiang 318050, P.R. China.
authors: Mei-Qin
authors: MQ
authors: Cai
authors: Luqiao Hospital of Taizhou Enze Medical Center (Group), Taizhou, Zhejiang 318050, P.R. China.
authors: Chun-Feng
authors: CF
authors: Bai
authors: Luqiao Hospital of Taizhou Enze Medical Center (Group), Taizhou, Zhejiang 318050, P.R. China.
authors: Xian-Fei
authors: XF
authors: Zhang
authors: Luqiao Hospital of Taizhou Enze Medical Center (Group), Taizhou, Zhejiang 318050, P.R. China.
authors: Li-Min
authors: LM
authors: Wang
authors: Luqiao Hospital of Taizhou Enze Medical Center (Group), Taizhou, Zhejiang 318050, P.R. China.
authors: Li
authors: L
authors: Lin
authors: Luqiao Hospital of Taizhou Enze Medical Center (Group), Taizhou, Zhejiang 318050, P.R. China.
authors: Shu-Zhen
authors: SZ
authors: Jia
authors: Luqiao Hospital of Taizhou Enze Medical Center (Group), Taizhou, Zhejiang 318050, P.R. China.
authors: Wen-Hua
authors: WH
authors: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000077204:Temozolomide
chemical_list: C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D003606:Dacarbazine; D000077204:Temozolomide