title: MiR-1224-5p acts as a tumor suppressor by targeting CREB1 in malignant gliomas.
abstract: The dysregulation of miR-1224-5p has been reported in several human cancers. However, the expression and function of miR-1224-5p in glioma remains unknown. The aim of our study was to investigate the effect of miR-1224-5p on glioma cells and to determine its functional signaling mediators. Using 198 glioma samples within the Chinese Glioma Genome Atlas expression dataset, we demonstrated that miR-1224-5p expression is decreased in high-grade gliomas when compared with low-grade gliomas. Differential miR-1224-5p expression in 50 randomly selected samples was verified by in situ hybridization. The expression of miR-1224-5p was shown to positively correlate with overall survival in 82 glioblastoma patients. Exogenous expression of miR-1224-5p in glioma cells suppressed proliferation and invasion and promoted apoptosis. Target prediction algorithms identified a consensus miR-1224-5p recognition site in the 3'UTR of the cAMP response element-binding protein (CREB1) gene, and this sequence was shown to directly confer miR-1224-5p repression in luciferase reporter assays. Furthermore, exogenous miR-1224-5p expression was shown to down-regulate CREB1, as well as its downstream target genes matrix metalloproteinase-9 and B-cell lymphoma-2. Conversely, over-expression of CREB1 reversed the effect of miR-1224-5p on the proliferation, invasion, and apoptosis of glioma cells. These data indicate that miR-1224-5p may inhibit tumor-associated activity in malignant gliomas by targeting CREB1.
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors: Jin
authors: J
authors: Qian
authors: Rui
authors: R
authors: Li
authors: Ying-Yi
authors: YY
authors: Wang
authors: Yan
authors: Y
authors: Shi
authors: Wen-Kang
authors: WK
authors: Luan
authors: Tao
authors: T
authors: Tao
authors: Jun-Xia
authors: JX
authors: Zhang
authors: Yi-Chang
authors: YC
authors: Xu
authors: Yong-Ping
authors: YP
authors: You
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C000603715:MIRN1224 microRNA, human; D035683:MicroRNAs
references: Am J Surg Pathol. 2012 Jul;36(7):e1-e11
references: 22510762
references: PLoS One. 2013 Oct 03;8(10):e76247
references: 24098452
references: PLoS One. 2013 Jun 21;8(6):e67581
references: 23805317
references: Clin Cancer Res. 2009 Apr 15;15(8):2583-7
references: 19351775
references: Cancer Lett. 2011 Jan 1;300(1):10-9
references: 20965651
references: Neoplasia. 2004 May-Jun;6(3):279-86
references: 15153340
references: Cancer Genet. 2012 Nov;205(11):545-51
references: 23098991
references: PLoS One. 2013 May 17;8(5):e63164
references: 23690991
references: J Cancer Res Clin Oncol. 2012 Apr;138(4):573-84
references: 22207524
references: Arch Neurol. 2010 Mar;67(3):279-83
references: 20212224
references: J Transl Med. 2012 Jun 08;10:119
references: 22681957
references: Int J Oncol. 2010 Jan;36(1):181-92
references: 19956847
references: Haematologica. 2014 Jan;99(1):116-24
references: 23975180
references: Neurosci Lett. 2004 Mar 11;357(3):223-6
references: 15003290
references: Acta Biochim Pol. 2012;59(4):467-74
references: 23173124
references: Am J Pathol. 2009 Nov;175(5):2197-206
references: 19815709
references: Nature. 2005 Jun 9;435(7043):834-8
references: 15944708
references: Int J Radiat Oncol Biol Phys. 2012 Jul 15;83(4):1113-9
references: 22172905
references: PLoS One. 2013;8(2):e57520
references: 23469012
references: Annu Rev Biochem. 1999;68:821-61
references: 10872467
references: Cancer Biol Ther. 2006 Jun;5(6):573-8
references: 16760647
references: RNA. 2013 Dec;19(12):1767-80
references: 24158791
references: Neurotherapeutics. 2009 Jul;6(3):447-57
references: 19560735
references: J Biol Chem. 2004 Apr 9;279(15):14803-11
references: 14742439
references: Genes Chromosomes Cancer. 2011 Aug;50(8):585-97
references: 21563230
references: Proc Natl Acad Sci U S A. 2012 Sep 25;109 (39):15805-10
references: 23019365
references: Nat Rev Mol Cell Biol. 2001 Aug;2(8):599-609
references: 11483993
references: Jpn J Clin Oncol. 2011 Feb;41(2):304-5
references: 21273379
references: J Biomed Sci. 2013 Oct 24;20:79
references: 24152184
references: J Biol Chem. 2006 Oct 6;281(40):29479-90
references: 16891311
references: Cancer Treat Res. 2013;158:119-37
references: 24222356
references: Eur J Clin Invest. 2006 May;36(5):353-61
references: 16634840
references: Cancer Res. 2009 Mar 15;69(6):2471-8
references: 19258499
references: Sci Rep. 2013;3:2739
references: 24061441
references: Mol Cell Biochem. 2013 Jul;379(1-2):51-8
references: 23543137
references: J Biol Chem. 2007 Feb 16;282(7):4794-802
references: 17150964
references: Cell Cycle. 2005 Sep;4(9):1179-84
references: 16096373
references: J Exp Clin Cancer Res. 2011 May 17;30:58
references: 21575270
references: Br J Cancer. 2007;96 Suppl:R40-4
references: 17393584