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MIR145 (microRNA 145)

Written2012-02Mohit Sachdeva, Yin Yuan Mo
Department of Radiation Oncology, Duke University Medical center, Durham, North Carolina-27710, USA (MS); Department of Medical Microbiology, Immunology, Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA (YYM)

(Note : for Links provided by Atlas : click)

Identity

Alias_namesMIRN145
Alias_symbol (synonym)hsa-mir-145
MIR-145
Other aliasmiR-145
miRNA145
HGNC (Hugo) MIR145
LocusID (NCBI) 406937
Atlas_Id 50927
Location 5q32  [Link to chromosome band 5q32]
Location_base_pair Starts at 149430646 and ends at 149430733 bp from pter ( according to hg19-Feb_2009)  [Mapping MIR145.png]

DNA/RNA

 
  Figure 1: A) Genomic localization of miR-145 gene on chromosome 5q32. B) Stem-loop structure of miR-145 (Red: mature miR-145 sequence).
Description miR-145 is located on chromosome 5 (5q32-33) within a 4.09 kb region (miRBase). The pri-microRNA structure of miR-145 has not been identified, yet it is suggested that it co-transcribed with miR-143. This gene has been implicated as both tumor and metastasis suppressor in multiple tumor types (Sachdeva and Mo, 2010a).
Transcription miR-145 is transcribed by RNA pol-II into pri-miRNA sequence, which is first processed to pre-miRNA (~88 bp long) involving RNA cutting and exporting, and finally to mature miR-145. miR-145 is a p53-regulated gene. Several reports suggest that miR-145 can be induced transcriptionally by p53 in response to stress such as serum starvation or anticancer drugs (Sachdeva et al., 2009; Spizzo et al., 2010). Interestingly, another report showed a novel mechanism of posttranscriptional regulation of miR-145 that occurs via p53-mediated RNA processing (Suzuki et al., 2009). Recently, a study demonstrates that activated Ras can suppress miR-143/145 cluster through Ras-responsive element-binding protein (RREB1), which represses the miR-143/145 promoter (Kent et al., 2010).
Pseudogene There is no pseudogene reported for this gene.

Protein

Note Non-coding RNA.

Mutations

Note No mutations have been found in mature miR-145 sequence; however, a study suggests that OVCAR8 (ovary) and NCI-H727 (lung) cells harbor mutations in pri-miR-145, i.e., C-133A/pri-microRNA/homozygous and G-5R (G/A)/pri-microRNA/heterozygous, respectively. Yet, these mutations do not have any effect on microRNA processing (Diederichs and Haber, 2006).

Implicated in

Note
  
Entity Cancer
Note Downregulation of miR-145 has been found in cancers of many tissue types including colon, breast, prostate, pancreas, etc. (Sachdeva et al., 2009; Bandres et al., 2006; Michael et al., 2003). For example, in situ hybridization detected accumulation of miR-145 in normal colon epithelia with no signal from adenocarcinomas cells. Loss of miR-145 in various tumors suggests its role as a tumor suppressor. In fact, miR-145 has been well documented as a tumor suppressor gene in multiple tumor types because of its anti-proliferative and pro-apoptotic effects. It is shown that miR-145 can negatively regulate multiple oncogenes such as MYC, Kras, IRS-1, ERK5, etc. involved in cell proliferation and survival (Sachdeva et al., 2009; Kent et al., 2010; Shi et al., 2007; Ibrahim et al., 2011).
  
  
Entity Metastasis
Note Several reports suggest that miR-145 is a suppressor of metastasis. For example, mir-145 negatively regulates MUC1 and suppresses invasion and metastasis of the breast cancer cells (Sachdeva and Mo, 2010b). Similar findings in prostate cancer and in gliomas have further confirmed the role of miR-145 as a metastasis suppressor by targeting genes including FASCN1 and SOX2, respectively (Fang et al., 2011; Watahiki et al., 2011; Leite et al., 2011).
  
  
Entity Stem cells and differentiation
Note A study has shown that miR-145 is induced during differentiation, and it directly silences the stem cell self renewal and pluripotency program by suppressing multiple pluripotent genes such as OCT4, SOX2 and KLF4 (Xu et al., 2009).
  
  
Entity Vascular smooth muscle cells
Note The role of miR-145 in differentiation of vascular smooth muscle cell (VSMC) has been recently investigated. A report demonstrated that miR-145 is the most enriched microRNA in arteries and its expression is significantly downregulated in vascular walls with neointimal lesions (Chen et al., 2004). Similarly, another group, using transgenic mouse model with miR-145 promoter fused to β-galactosidase gene, found that miR-145 is cardiac-specific and smooth-muscle specific microRNA regulated by serum response factor, myocardin and Nkx2-5 (NK2 transcription factor related, locus 5) (Cordes et al., 2009). Further evidence from the miR-43/miR-145 KO rats suggests that this microRNA cluster is expressed mostly in the SMC compartment in vessels and SMC-containing organs and their loss induces an incomplete differentiation of VSMCs (Elia et al., 2009).
  
  
Entity 5q syndrome
Note A comprehensive study using clinical samples combined with mouse models have found that deletion of chromosome 5q correlates with loss of two miRNAs that are abundant in hematopoietic stem/progenitor cells (HSPCs), miR-145 and miR-146a. In addition, they observed that miR-145 is highly expressed in primitive lin- (mouse) and CD34+ (human) bone marrow cells than committed cells and stable knockdown of miR-145 in these cells in mouse marrow results in 5-q syndrome (Starczynowski et al., 2010). Similar work from another group in patients with del (5q) have decreased expression of miR-145 and increased expression of Fli-1 (Kumar et al., 2011). They found that miR-145 functions through repression of Fli-1, a megakaryocyte and erythroid regulatory transcription factor and thus, cells lacking miR-145 have impaired megakaryocyte and erythroid differentiation.
  

Bibliography

Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues.
Bandres E, Cubedo E, Agirre X, Malumbres R, Zarate R, Ramirez N, Abajo A, Navarro A, Moreno I, Monzo M, Garcia-Foncillas J.
Mol Cancer. 2006 Jul 19;5:29.
PMID 16854228
 
MicroRNAs modulate hematopoietic lineage differentiation.
Chen CZ, Li L, Lodish HF, Bartel DP.
Science. 2004 Jan 2;303(5654):83-6. Epub 2003 Dec 4.
PMID 14657504
 
miR-145 and miR-143 regulate smooth muscle cell fate and plasticity.
Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee TH, Miano JM, Ivey KN, Srivastava D.
Nature. 2009 Aug 6;460(7256):705-10. Epub 2009 Jul 5.
PMID 19578358
 
Sequence variations of microRNAs in human cancer: alterations in predicted secondary structure do not affect processing.
Diederichs S, Haber DA.
Cancer Res. 2006 Jun 15;66(12):6097-104.
PMID 16778182
 
The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease.
Elia L, Quintavalle M, Zhang J, Contu R, Cossu L, Latronico MV, Peterson KL, Indolfi C, Catalucci D, Chen J, Courtneidge SA, Condorelli G.
Cell Death Differ. 2009 Dec;16(12):1590-8. Epub 2009 Oct 9.
PMID 19816508
 
The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis.
Fang X, Yoon JG, Li L, Yu W, Shao J, Hua D, Zheng S, Hood L, Goodlett DR, Foltz G, Lin B.
BMC Genomics. 2011 Jan 6;12:11.
PMID 21211035
 
MicroRNA replacement therapy for miR-145 and miR-33a is efficacious in a model of colon carcinoma.
Ibrahim AF, Weirauch U, Thomas M, Grunweller A, Hartmann RK, Aigner A.
Cancer Res. 2011 Aug 1;71(15):5214-24. Epub 2011 Jun 20.
PMID 21690566
 
Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway.
Kent OA, Chivukula RR, Mullendore M, Wentzel EA, Feldmann G, Lee KH, Liu S, Leach SD, Maitra A, Mendell JT.
Genes Dev. 2010 Dec 15;24(24):2754-9.
PMID 21159816
 
Coordinate loss of a microRNA and protein-coding gene cooperate in the pathogenesis of 5q- syndrome.
Kumar MS, Narla A, Nonami A, Mullally A, Dimitrova N, Ball B, McAuley JR, Poveromo L, Kutok JL, Galili N, Raza A, Attar E, Gilliland DG, Jacks T, Ebert BL.
Blood. 2011 Oct 27;118(17):4666-73. Epub 2011 Aug 26.
PMID 21873545
 
MicroRNA expression profiles in the progression of prostate cancer-from high-grade prostate intraepithelial neoplasia to metastasis.
Leite KR, Tomiyama A, Reis ST, Sousa-Canavez JM, Sanudo A, Camara-Lopes LH, Srougi M.
Urol Oncol. 2011 Aug 29. [Epub ahead of print]
PMID 21880514
 
Reduced accumulation of specific microRNAs in colorectal neoplasia.
Michael MZ, O' Connor SM, van Holst Pellekaan NG, Young GP, James RJ.
Mol Cancer Res. 2003 Oct;1(12):882-91.
PMID 14573789
 
MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1.
Sachdeva M, Mo YY.
Cancer Res. 2010b Jan 1;70(1):378-87. Epub 2009 Dec 8.
PMID 19996288
 
Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells.
Shi B, Sepp-Lorenzino L, Prisco M, Linsley P, deAngelis T, Baserga R.
J Biol Chem. 2007 Nov 9;282(45):32582-90. Epub 2007 Sep 7.
PMID 17827156
 
miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-alpha in human breast cancer cells.
Spizzo R, Nicoloso MS, Lupini L, Lu Y, Fogarty J, Rossi S, Zagatti B, Fabbri M, Veronese A, Liu X, Davuluri R, Croce CM, Mills G, Negrini M, Calin GA.
Cell Death Differ. 2010 Feb;17(2):246-54. Epub 2009 Sep 4.
PMID 19730444
 
Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype.
Starczynowski DT, Kuchenbauer F, Argiropoulos B, Sung S, Morin R, Muranyi A, Hirst M, Hogge D, Marra M, Wells RA, Buckstein R, Lam W, Humphries RK, Karsan A.
Nat Med. 2010 Jan;16(1):49-58. Epub 2009 Nov 8.
PMID 19898489
 
Modulation of microRNA processing by p53.
Suzuki HI, Yamagata K, Sugimoto K, Iwamoto T, Kato S, Miyazono K.
Nature. 2009 Jul 23;460(7254):529-33.
PMID 19626115
 
MicroRNAs associated with metastatic prostate cancer.
Watahiki A, Wang Y, Morris J, Dennis K, O'Dwyer HM, Gleave M, Gout PW, Wang Y.
PLoS One. 2011;6(9):e24950. Epub 2011 Sep 30.
PMID 21980368
 
MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells.
Xu N, Papagiannakopoulos T, Pan G, Thomson JA, Kosik KS.
Cell. 2009 May 15;137(4):647-58. Epub 2009 Apr 30.
PMID 19409607
 

Citation

This paper should be referenced as such :
Sachdeva, M ; Mo, YY
MIR145 (microRNA 145)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(7):485-487.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/MIR145ID50927ch5q32.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  Classification of myelodysplastic syndromes 2015


External links

Nomenclature
HGNC (Hugo)MIR145   31532
Cards
AtlasMIR145ID50927ch5q32
Entrez_Gene (NCBI)MIR145  406937  microRNA 145
AliasesMIRN145; miR-145; miRNA145
GeneCards (Weizmann)MIR145
Ensembl hg19 (Hinxton)ENSG00000276365 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000276365 [Gene_View]  chr5:149430646-149430733 [Contig_View]  MIR145 [Vega]
ICGC DataPortalENSG00000276365
TCGA cBioPortalMIR145
AceView (NCBI)MIR145
Genatlas (Paris)MIR145
WikiGenes406937
SOURCE (Princeton)MIR145
Genetics Home Reference (NIH)MIR145
miRBaseMIR145
dbDEMCMIR145
Genomic and cartography
GoldenPath hg38 (UCSC)MIR145  -     chr5:149430646-149430733 +  5q32   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MIR145  -     5q32   [Description]    (hg19-Feb_2009)
EnsemblMIR145 - 5q32 [CytoView hg19]  MIR145 - 5q32 [CytoView hg38]
Mapping of homologs : NCBIMIR145 [Mapview hg19]  MIR145 [Mapview hg38]
OMIM611795   
Gene and transcription
Genbank (Entrez)AJ535835 LM608501
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)MIR145
Alternative Splicing GalleryENSG00000276365
Gene ExpressionMIR145 [ NCBI-GEO ]   MIR145 [ EBI - ARRAY_EXPRESS ]   MIR145 [ SEEK ]   MIR145 [ MEM ]
Gene Expression Viewer (FireBrowse)MIR145 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)406937
GTEX Portal (Tissue expression)MIR145
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)MIR145
DMDM Disease mutations406937
Blocks (Seattle)MIR145
Human Protein AtlasENSG00000276365
Protein Interaction databases
FunCoupENSG00000276365
BioGRIDMIR145
STRING (EMBL)MIR145
ZODIACMIR145
Ontologies - Pathways
Huge Navigator MIR145 [HugePedia]
snp3D : Map Gene to Disease406937
BioCentury BCIQMIR145
ClinGenMIR145
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD406937
Chemical/Pharm GKB GenePA164722494
Clinical trialMIR145
Miscellaneous
canSAR (ICR)MIR145 (select the gene name)
Probes
Litterature
PubMed290 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMIR145
EVEXMIR145
GoPubMedMIR145
iHOPMIR145
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon May 22 09:16:23 CEST 2017

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