title: Tumor-suppressive microRNA-1291 directly regulates glucose transporter 1 in renal cell carcinoma.
abstract: Our recent studies of microRNA (miRNA) expression signatures demonstrated that microRNA-1291 (miR-1291) was significantly downregulated in renal cell carcinoma (RCC) clinical specimens and was a putative tumor-suppressive miRNA in RCC. The aim of the present study was to investigate the functional significance of miR-1291 in cancer cells and to identify novel miR-1291-mediated cancer pathways and target genes in RCC. Expression of miR-1291 was significantly downregulated in RCC tissues compared with adjacent non-cancerous tissues. Restoration of mature miR-1291 in RCC cell lines (A498 and 786-O) revealed significant inhibition of cell proliferation, migration and invasion, suggesting that miR-1291 functioned as a tumor suppressor. To identify miR-1291-mediated molecular pathways and targets, we used gene expression analysis (expression of RCC clinical specimens and miR-1291-transfected A498 cells) and in silico database analysis. Our data demonstrated that 79 signaling pathways were significantly regulated by tumor-suppressive miR-1291 in RCC cells. Moreover, solute career family 2 member 1 (SLC2A1) was a candidate target of miR-1291 regulation. The SLC2A1 gene provides instructions for producing glucose transporter protein type 1 (GLUT1). Luciferase reporter assays showed that miR-1291 directly regulated SLC2A1/GLUT1. In RCC clinical specimens, the expression of SLC2A1/GLUT1 mRNA was significantly higher in cancer tissues than in non-cancerous tissues. A significant inverse correlation was recognized between SLC2A1/GLUT1 and miR-1291 expression (r = -0.55, P < 0.0001). Loss of tumor-suppressive miR-1291 enhanced RCC cell proliferation, migration and invasion through targeting SLC2A1/GLUT1. The identification of novel tumor-suppressive miR-1291-mediated molecular pathways and targets has provided new insights into RCC oncogenesis and metastasis.
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yoshino
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Itesako
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Yamada
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tatarano
authors.forename: Hideo
authors.initials: H
authors.lastname: Hidaka
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yonezawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D051272:Glucose Transporter Type 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D059467:Transcriptome
chemical_list: D051272:Glucose Transporter Type 1; C587958:MIRN1291 microRNA, human; D035683:MicroRNAs; C495677:SLC2A1 protein, human
references.citation: Cancer. 1993 Nov 15;72(10):2979-85
references.pmid: 8221565
references.citation: Cancer Sci. 2013 Nov;104(11):1411-9
references.pmid: 23889809
references.citation: Clin Med Insights Oncol. 2010 Dec 19;4:143-54
references.pmid: 21234295
references.citation: Genes Cancer. 2010 Nov;1(11):1100-14
references.pmid: 21533017
references.citation: Nat Rev Cancer. 2006 Apr;6(4):259-69
references.pmid: 16557279
references.citation: Cancer Treat Rev. 2008 May;34(3):193-205
references.pmid: 18313224
references.citation: Int J Oncol. 2011 Jan;38(1):209-17
references.pmid: 21109942
references.citation: Science. 2009 May 22;324(5930):1029-33
references.pmid: 19460998
references.citation: Cancer Res. 2011 Dec 1;71(23):7291-300
references.pmid: 21987722
references.citation: Nat Rev Genet. 2004 Apr;5(4):316-23
references.pmid: 15131654
references.citation: Mol Cancer Ther. 2008 Dec;7(12):3655-60
references.pmid: 19074842
references.citation: Urol Oncol. 2009 May-Jun;27(3):238-45
references.pmid: 19414111
references.citation: Mol Membr Biol. 2001 Oct-Dec;18(4):247-56
references.pmid: 11780753
references.citation: Sci Transl Med. 2011 Aug 3;3(94):94ra70
references.pmid: 21813754
references.citation: Int J Oncol. 2012 Sep;41(3):805-17
references.pmid: 22766839
references.citation: J Breast Cancer. 2012 Jun;15(2):172-80
references.pmid: 22807934
references.citation: Clin Cancer Res. 2012 Jul 15;18(14):3961-3971
references.pmid: 22573349
references.citation: Am J Clin Pathol. 2007 Aug;128(2):245-54
references.pmid: 17638658
references.citation: Int J Cancer. 1994 Mar 1;56(5):622-9
references.pmid: 8314336
references.citation: J Urol. 1995 Mar;153(3 Pt 1):798-801
references.pmid: 7861542
references.citation: Cancer Sci. 2013 Mar;104(3):304-12
references.pmid: 23176581
references.citation: Nat Rev Genet. 2008 Feb;9(2):102-14
references.pmid: 18197166
references.citation: Science. 2001 Apr 20;292(5516):468-72
references.pmid: 11292861
references.citation: Br J Cancer. 2010 Mar 2;102(5):883-91
references.pmid: 20160723
references.citation: J Cell Physiol. 2005 Mar;202(3):654-62
references.pmid: 15389572
references.citation: Cancer. 2001 Sep 1;92(5):1144-50
references.pmid: 11571727
references.citation: Cancer. 2001 Aug 1;92(3):634-41
references.pmid: 11505409
references.citation: Mol Aspects Med. 2010 Feb;31(1):60-74
references.pmid: 19995572
references.citation: Cell. 2004 Jan 23;116(2):281-97
references.pmid: 14744438
references.citation: Oncotarget. 2012 Jan;3(1):44-57
references.pmid: 22294552
references.citation: Hum Pathol. 2000 Jan;31(1):11-22
references.pmid: 10665907
references.citation: Nat Rev Cancer. 2002 Sep;2(9):673-82
references.pmid: 12209156
references.citation: Am J Clin Pathol. 2003 Nov;120(5):691-8
references.pmid: 14608894
references.citation: Science. 1956 Feb 24;123(3191):309-14
references.pmid: 13298683
references.citation: Eur J Cancer. 2012 Apr;48(6):827-36
references.pmid: 21745735