title: MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells.
abstract: miR-7 (microRNA-7) has been characterized as a tumour suppressor in several human cancers. It targets a number of proto-oncogenes that contribute to cell proliferation and survival. However, the mechanism(s) by which miR-7 suppresses tumorigenesis in TSCC (tongue squamous cell carcinoma) is unknown. The present bioinformatics analysis revealed that IGF1R (insulin-like growth factor 1 receptor) mRNA is a potential target for miR-7. Ectopic transfection of miR-7 led to a significant reduction in IGF1R at both the mRNA and protein levels in TSCC cells. Knockdown of miR-7 in TSCC cells enhanced IGF1R expression. Direct targeting of miR-7 to three candidate binding sequences located in the 3'-untranslated region of IGF1R mRNA was confirmed using luciferase-reporter-gene assays. The miR-7-mediated down-regulation of IGF1R expression attenuated the IGF1 (insulin-like growth factor 1)-induced activation of Akt (protein kinase B) in TSCC cell lines, which in turn resulted in a reduction in cell proliferation and cell-cycle arrest, and an enhanced apoptotic rate. Taken together, the present results demonstrated that miR-7 regulates the IGF1R/Akt signalling pathway by post-transcriptional regulation of IGF1R. Our results indicate that miR-7 plays an important role in TSCC and may serve as a novel therapeutic target for TSCC patients.
authors.affiliation: Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, 60612, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Liu
authors.forename: Zujian
authors.initials: Z
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Heidbreder
authors.forename: Antonia
authors.initials: A
authors.lastname: Kolokythas
authors.forename: Anxun
authors.initials: A
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Dai
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D007334:Insulin-Like Growth Factor I; D008156:Luciferases; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D017526:Receptor, IGF Type 1; C549242:MIRN7-1 microRNA, human
references.citation: Invasion Metastasis. 1998-1999;18(5-6):219-28
references.pmid: 10729767
references.citation: Genome Res. 2009 Jan;19(1):92-105
references.pmid: 18955434
references.citation: CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49
references.pmid: 19474385
references.citation: Nat Genet. 2005 Jul;37(7):766-70
references.pmid: 15965474
references.citation: J Biol Chem. 2009 Feb 27;284(9):5731-41
references.pmid: 19073608
references.citation: Comp Funct Genomics. 2009;:837514
references.pmid: 19753298
references.citation: CA Cancer J Clin. 2005 Jan-Feb;55(1):10-30
references.pmid: 15661684
references.citation: Cancer Genomics Proteomics. 2009 May-Jun;6(3):131-9
references.pmid: 19487542
references.citation: Cell. 2003 Dec 26;115(7):787-98
references.pmid: 14697198
references.citation: Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4330-5
references.pmid: 9113989
references.citation: Nature. 2005 Mar 17;434(7031):338-45
references.pmid: 15735639
references.citation: Cancer Genomics Proteomics. 2008 Mar-Apr;5(2):85-94
references.pmid: 18460737
references.citation: Science. 2008 Mar 28;319(5871):1789-90
references.pmid: 18369137
references.citation: Cancer Res. 2008 Oct 15;68(20):8195-200
references.pmid: 18922890
references.citation: Cancer Res. 2008 May 15;68(10):3566-72
references.pmid: 18483236
references.citation: Cell. 2005 Jan 14;120(1):15-20
references.pmid: 15652477
references.citation: Int J Cancer. 2010 Aug 1;127(3):505-12
references.pmid: 20232393
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Cancer Lett. 2009 Dec 28;286(2):217-22
references.pmid: 19540661
references.citation: Clin Cancer Res. 2008 May 1;14(9):2588-92
references.pmid: 18451220
references.citation: Oncol Res. 2010;18(8):377-85
references.pmid: 20441052