Department of Nuerology (Wen GL,Zhang BCH,Wen CHM),Department of Onclogy (Wan LX,Zhang JW,Liu Y),Department of Radiation Oncology (Wang Y,Zhang K,Rao SHL),Nanyang Central Hospital, Nanyang Hospital Affiliated to Zhengzhou University,Nanyang 473009,China
Abstract：Objective To investigate the signaling pathway probably targeted by miR-206 in regulation of the radiosensitivity of glioma cells, and to provide a basis for further understanding of its regulatory mechanism. Methods The miR-206 mimic or miR-206 inhibitor was transfected into U87 glioma cells. The activity of the MAPK pathway was inhibited by PD98059. The cells were exposed to radiation. MTT assay and colony formation assay were used to determine the changes in the radiosensitivity of cells. Quantitative RT-PCR and Western blot were used to determine the expression of miR-206 and MAPK1, respectively. TargetScan prediction and dual luciferase reporter system were used to verify the interaction between miR-206 and MAPK1. Results After exposure to radiation, the glioma cells had downregulated expression of miR-206 and upregulated expression of MAPK1. Overexpression of miR-206 induced by the miR-206 mimic reduced cell proliferation and colony formation ability and enhanced the radiosensitivity;inhibition of miR-206 expression by the miR-206 inhibitor reversed the effects of the miR-206 mimic. MAPK1 was predicted to be the possible target gene of miR-206 by TargetScan software. The dual luciferase reporter assay further confirmed the interaction between miR-206 and MAPK1. The expression of MAPK1 was negatively correlated with that of miR-206. The radiosensitivity of glioma cells was enhanced when the MAPK pathway was blocked by the inhibitor. Conclusions miR-206 probably targets MAPK1. It may regulate the radiosensitivity of glioma cells by inhibiting the activity of the MAPK signaling pathway.
Wen Gongling,Zhang Baochao,Wan Lixin et al. miR-206 enhances radiosensitivity of glioma cells by targeting MAPK1 pathway[J]. Chinese Journal of Radiation Oncology, 2016, 25(7): 759-763.
[1]Chang L,Su J,Jia XZ,et al. Treating malignant glioma in Chinese patients:update on temozolomide[J].Onco Targets Ther,2014,7:235-244.DOI:10.2147/OTT.S41336 [2]He L,Hannon GJ.MicroRNAs:small RNAs with a big role in gene regulation[J].Nat Rev Genet,2004,5(7):522-531.DOI:10.1038/nrg1379 [3]Zhao LQ,Lu XB,Cao Y.MicroRNA and signal transduction pathways in tumor radiation response[J].Cell Signal,2013,25(7):1625-1634.DOI:10.1016/j.cellsig.2013.04.004 [4]Upadhya D,Ogata M,Reneker LW.MAPK1 is required for establishing the pattern of cell proliferation and for cell survival during lens development[J].Development,2013,140(7):1573-1582.DOI:10.1242/dev.081042 [5]Zhao LQ,Bode AM,Cao Y,et al. Regulatory mechanisms and clinical perspectives of miRNA in tumor radiosensitivity[J].Carcinogenesis,2012,33(11):2220-2227.DOI:10.1093/carcin/bgs235 [6]Gwak HS,Kim TH,Jo GH,et al. Silencing of microRNA-21 confers radio-sensitivity through inhibition of the PI3K/AKT pathway and enhancing autophagy in malignant glioma cell lines[J].PLoS One,2012,7(10):e47449.DOI:10.1371/journal.pone.0047449 [7]Chen G,Zhu W,Shi D,et al. MicroRNA-181a sensitizes human malignant glioma U87MG cells to radiation by targeting Bcl-2[J].Oncol Rep,2010,23(4):997-1003.DOI:10.3892/or_00000725 [8]Asuthkar S,Velpula KK,Chetty C,et al. Epigenetic regulation of miRNA-211 by MMP-9 governs glioma cell apoptosis,chemosensitivity and radiosensitivity[J].Oncotarget,2012,3(11):1439-1454.DOI:10.18632/oncotarget.683 [9]Guo P,Lan J,Ge JW,et al. MiR-26a enhances the radiosensitivity of glioblastoma multiforme cells through targeting of ataxia–telangiectasia mutated[J].Exp Cell Res,2014,320(2):200-208.DOI:10.1016/j.yexcr.2013.10.020 [10]Adams BD,Cowee DM,White BA.The role of miR-206 in the epidermal growth factor (EGF) induced repression of estrogen receptor-α(ERα) signaling and a luminal phenotype in MCF-7 breast cancer cells[J].Mol Endocrinol,2009,23(8):1215-1230.DOI:10.1210/me.2009-0062 [11]Kondo N,Toyama T,Sugiura H,et al.miR-206 Expression is down-regulated in estrogen receptor α–positive human breast cancer[J].Cancer Res,2008,68(13):5004-5008.DOI:10.1158/0008-5472.CAN-08-0180 [12]Tavazoie SF,Alarcón C,Oskarsson T,et al. Endogenous human microRNAs that suppress breast cancer metastasis[J].Nature,2008,451(7175):147-152.DOI:10.1038/nature06487 [13]Zhou J,Tian Y,Li J,et al.miR-206 is down-regulated in breast cancer and inhibits cell proliferation through the up-regulation of cyclinD2[J].Biochem Biophys Res Commun,2013,433(2):207-212.DOI:10.1016/j.bbrc.2013.02.084 [14]Song GS,Zhang YX,Wang L.MicroRNA-206 targets notch3,activates apoptosis,and inhibits tumor cell migration and focus formation[J].J Biol Chem,2009,284(46):31921-31927.DOI:10.1074/jbc. M109.046862 [15]Williams TM,Flecha AR,Keller P,et al. Cotargeting MAPK and PI3K signaling with concurrent radiotherapy as a strategy for the treatment of pancreatic cancer[J].Mol Cancer Ther,2012,11(5):1193-1202.DOI:10.1158/1535-7163.MCT-12-0098 [16]Kumar P,Miller AI,Polverini PJ.p38 MAPK mediates γ-irradiation-induced endothelial cell apoptosis,and vascular endothelial growth factor protects endothelial cells through the phosphoinositide 3-kinase-Akt-Bcl-2 pathway[J].J Biol Chem,2004,279(41):43352-43360.DOI:10.1074/jbc. M405777200 [17]Vrana JA,Grant S,Dent P.Inhibition of the MAPK pathway abrogates BCL2-mediated survival of leukemia cells after exposure to low-dose ionizing radiation[J].Radiat Res,1999,151(5):559-569.DOI:10.2307/3580032 [18]Sun KK,Zhong N,Yang Y,et al. Enhanced radiosensitivity of NSCLC cells by transducer of erbB2.1(TOB1) through modulation of the MAPK/ERK pathway[J].Oncol Rep, 2013,29(6):2385-2391.DOI:10.3892/or.2013.2403 [19]Marampon F,Gravina GL,Di Rocco A,et al. MEK/ERK inhibitor U0126 increases the radiosensitivity of rhabdomyosarcoma cells in vitro and in vivo by downregulating growth and DNA repair signals[J].Mol Cancer Ther,2011,10(1):159-168.DOI:10.1158/1535-7163.MCT-10-0631.
2016, Vol. 25 
