title: MiR-30a-5p antisense oligonucleotide suppresses glioma cell growth by targeting SEPT7.
abstract: MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by targeting the mRNAs of hundreds of human genes. Variations in miRNA expression levels were shown to be associated with glioma. We have previously found miR-30a-5p overexpression in glioma cell lines and specimens. Bioinformatics analyses predict that several miRNAs, including miR-30a-5p, are involved in the post-transcriptional regulation of SEPT7. SEPT7 is a member of the septin family, which is a highly conserved subfamily of GTPases implicated in exocytosis, apoptosis, synaptogenesis, neurodegeneration and tumorigenesis. Our previous study has also demonstrated that SEPT7 expression is decreased in astrocytic gliomas with different grades and plays a tumor suppressor role. In the present study, we knocked down miR-30a-5p with antisense oligonucleotide (miR-30a-5p AS) in LN229 and SNB19 glioblastoma(GBM) cells, and found that cell growth and invasion were inhibited, while apoptosis was induced. miR-30a-5p AS treated cells showed upregulation of SEPT7 and downregulation of PCNA, cyclin D1, Bcl2, MMP2 and MMP9. In contrast, when miR-30a-5p mimics were transfected into LN229 and SNB19 GBM cells, cell growth and invasion were promoted and the expression of relevant proteins increased. Meanwhile, the effect of miR-30a-5p mimics on glioma cells can be reversed by transfection of SEPT7 construct. Additionaly, miR-30a-5p directly targeting SEPT7 was identified by the reporter gene assay. Our study demonstrates,for the first time, that miR-30a-5p is a bona fide negative regulator of SEPT7 and the oncogenic activity of miR-30a-5p in human gliomas is at least in part through the repression of SEPT7.
authors: Department of Neurosurgery, Tianjin Medical University, General Hospital, Tianjin Neurolgical Institute, Laboratory of Neuro-Oncology, Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, People's Republic of China.
authors: Zhifan
authors: Z
authors: Jia
authors: Kun
authors: K
authors: Wang
authors: Guangxiu
authors: G
authors: Wang
authors: Anling
authors: A
authors: Zhang
authors: Peiyu
authors: P
authors: Pu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D058112:Septins / Q000172:deficiency / Q000235:genetics*; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; C113158:SEPTIN7 protein, human; D058112:Septins
references: Algorithms Mol Biol. 2008 Dec 22;3:16
references: 19102780
references: J Cell Sci. 2001 Mar;114(Pt 5):839-44
references: 11181167
references: Biochem Biophys Res Commun. 2005 Sep 9;334(4):1351-8
references: 16039986
references: J Neurosci Methods. 1998 Dec 31;86(1):63-9
references: 9894786
references: Mol Cancer Res. 2003 Oct;1(12):882-91
references: 14573789
references: Biomark Insights. 2006;2:113-121
references: 18079988
references: Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2008 Jun;25(3):262-7
references: 18543212
references: Cancer Res. 2004 Jun 1;64(11):3753-6
references: 15172979
references: Gut. 2010 May;59(5):579-85
references: 19951901
references: Oncogene. 2006 Apr 20;25(17):2537-45
references: 16331254
references: Horm Metab Res. 2009 Jun;41(6):475-81
references: 19370508
references: Oncogene. 2007 Nov 29;26(54):7590-5
references: 17563749
references: Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19075-80
references: 16365291
references: Biochem Biophys Res Commun. 1994 Jul 15;202(1):82-7
references: 8037772
references: Cancer Res. 2005 Aug 15;65(16):7065-70
references: 16103053
references: Oncol Rep. 2010 Jun;23(6):1625-33
references: 20428818
references: Genes Chromosomes Cancer. 2004 Feb;39(2):167-9
references: 14695998
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: Mol Ther. 2007 Dec;15(12):2070-9
references: 17878899
references: Annu Rev Pathol. 2006;1:97-117
references: 18039109
references: Carcinogenesis. 2012 Apr;33(4):732-9
references: 22287560
references: J Neurooncol. 2010 Jul;98(3):329-40
references: 20035367