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MIR146B (microRNA 146b)

Written2012-12Amandine Garcia, Sylvie Mazoyer
CNRS UMR5286 Inserm U1052, Universite Lyon 1, Cancer Research Centre of Lyon, Centre Leon Berard, Lyon, France

(Note : for Links provided by Atlas : click)

Identity

Alias_namesMIRN146B
Alias_symbol (synonym)hsa-mir-146b
Other aliasmiRNA146B
HGNC (Hugo) MIR146B
LocusID (NCBI) 574447
Atlas_Id 50855
Location 10q24.32  [Link to chromosome band 10q24]
Location_base_pair Starts at 102436512 and ends at 102436584 bp from pter ( according to hg19-Feb_2009)  [Mapping MIR146B.png]
Local_order Based on Mapviewer, gene flanking MIR146B oriented from centromere to telomere on 10q24.32 are:
- NFKB2: Nuclear factor of kappa light polypeptide gene enhancer in B-cell 2
- PSD: pleckstrin and Sec7 domain containing
- FBXL15: F-box and leucine-rich repeat protein 15
- CUEDC2: CUE domain containing 2
- MIR146B: microRNA 146b
- LOC100505761: hypothetical LOC100505761
- TMEM180: transmembrane protein 180
- ACTR1A: ARP1 actin-related protein 1 homolog A
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

Note The MIR146B gene is transcribed into a precursor that produces two mature microRNAs, miR-146b-5p and miR-146b-3p. These microRNAs belong to the miR-146 family, which comprises 2 other members, miR-146a-5p and miR-146a* (recently renamed miR-146a-3p) produced from a gene, MIR146A, localized on chromosome 5.
 
  A. Homo sapiens stem-loop structure of pre-miR-146b. This figure represents the sequence and structure of the miR-146b precursor (pre-miR-146b). Two different mature miRNAs are produced from this precursor: miR-146b-5p (sequence in blue) and miR-146b-3p (sequence in pink). The orientations 5' to 3' are indicated by the direction of the arrows. B. The miR-146 family members. Identities between the sequences of miR-146a-5p and miR-146b-5p are shown in orange and those between the sequences of miR-146a-3p and miR-146b-3p are shown in green. MiR-146a-5p and miR-146b-5p differ by only two nucleotides located outside the seed region, while miR-146a-3p and miR-146b-3p are much more divergent, especially in the seed region.
Description MIR146B is located in an intergenic region.
Transcription RNA Polymerase II is suggested to be the most likely enzyme involved in microRNA transcription, leading to the production of a ~1000 nucleotide primary microRNA, in this case pri-miR-146b. The beginning and the end of the pri-miR-146b sequence are unknown.

pre-miR-146b
miRBase accession number: MI0003129.
Length: 73 nucleotides.
Sequence: 5'-CCUGGCACUGAGAACUGAAUUCCAUAGGCUGUGAGCUCUAGCAAUGCCCUGUGGACUCAGUUCUGGUGCCCGG-3'

mature miR-146b-5p
miRBase accession number: MIMAT0002809.
Length: 22 nucleotides.
Sequence: 5'-UGAGAACUGAAUUCCAUAGGCU-3'

mature miR-146b-3p
miRBase accession number: MIMAT0004766.
Length: 22 nucleotides.
Sequence: 5'-UGCCCUGUGGACUCAGUUCUGG-3'

Pseudogene No reported pseudogenes.

Protein

Note microRNAs aren't translated into amino acids.

Mutations

Note The 1000 Genome project identified a SNV (single nucleotide variation) in one West African individual, a C>T variation at position 104196269 (according to hg19-Feb_2009) in the first nucleotide of pre-miR-146b. The minor allele frequency is 0.059 in 118 individual samples of a West Africa population. This variation is reported in the NCBI SNP database and referenced with the number rs76149940 (submission in March 2010).

Implicated in

Note
  
Entity Breast cancer
Prognosis mir-146b-5p along with other microRNAs may permit to differentiate breast tumour sub-types. However, conflicting results have been obtained. One study, where miR-146b has been analysed in 167 breast cancer cases, showed an elevated expression in triple negative breast tumours. This study comprised analyses of several different tumour mammary cell lines and miR-146b-5p was found to be the most expressed in basal-like tumour cell lines (Garcia et al., 2011).
A second study, based on 20 samples only, identified specific expression of a set of seven microRNAs (including miR-146b-5p) in normal basal cells but not in basal-like breast cancers, which are close to triple negative breast cancers. miR-146b-5p may have an elevated expression in malignant myoepithelioma of the breast (Bockmeyer et al., 2011).
Oncogenesis Two studies described a biological role for miR-146b in breast tumour progression. The BRMS1 (Breast cancer Metastasis Suppressor 1) protein up-regulated the expression of miR-146b in MDA-MB-435, a tumour mammary cell line. Moreover, the overexpression of this microRNA down-regulated the expression of EGFR (Epidermal Growth Factor Receptor) in another tumour cell line, MDA-MB-231. This study showed an impact, in vitro, of miR-146b on invasion and migration of cells and on the suppression of metastasis (Bockmeyer et al., 2011).
The second study depicted a direct target of miR-146b-5p, BRCA1 (BReast CAncer 1), one of the two major breast cancer predisposition genes. The binding of miR-146-5p to the BRCA1 3'UTR decreased the expression of BRCA1, induced cellular proliferation and reduced the homologous recombination rate. miR-146b seemed to have an important role in tumour progression via BRCA1 (Garcia et al., 2011).
  
  
Entity Thyroid cancer
Disease Three studies showed that miR-146b, along with a set of other microRNAs, are overexpressed in tumours versus hyperplasic nodules or versus uncertain malignant potential tumours (Nikiforova et al., 2008; Lassalle et al., 2011; Chen et al., 2008). miR-146b is consistently overexpressed in both papillary and follicular thyroid carcinomas (Chen et al., 2008) and is associated with extrathyroidal invasion (Chou et al., 2010) and with aggressive papillary thyroid carcinoma (Yip et al., 2011). Of note, in these two studies, miR-146b overexpression seems correlated with BRAF mutations.
Prognosis The expression of miR-146b and of a set of six other microRNAs was able to predict malignancy of thyroid fine needle aspiration specimens (Shen et al., 2012; Agretti et al., 2012).
Oncogenesis In thyroid follicular cells, miR-146b-5p was shown to bind directly the 3'UTR of SMAD4, an important member of the TGF-β signalling pathway. This modulation of the TGF-β signal confirmed the oncogenic role of miR-146b-5p in thyroid cancers (Geraldo et al., 2012).
  
  
Entity Lung cancer
Prognosis A microarray analysis of 61 squamous cell carcinoma samples versus 10 normal lung samples showed that miR-146b had the strongest prediction accuracy for stratifying Non-Small Cell Lung Cancer (NSCLC) in prognostic groups (Raponi et al., 2009). Another study completed this observation and found a significant reduction of a set of seven microRNAs (including miR-146b) in serum of NSCLC patients (Heegaard et al., 2012).
Oncogenesis A study analysed the effect of miR-146b overexpression in A549 lung cancer cells. A 3-8-fold increase in the expression of pre-miR-146b did not alter the major cellular functions classically involved in oncogenesis, such as proliferation, migration or invasiveness. This overexpression only impacted the ability to form colonies, perhaps because miR-146b-5p and miR-146b-3p may have opposing effects (Patnaik et al., 2011).
  
  
Entity Other cancers
Note (like prostate, pancreas, kidney, colorectal)
Disease microRNA profiling by microarrays has shown that miR-146b is overexpressed in many cancer types, such as glioma (Xia et al., 2009), melanoma (Jukic et al., 2010), oesophageal cancer (Zhao et al., 2012), bladder cancer (Pignot et al., 2012), colorectal cancer (Ragusa et al., 2010) or oral cancers (Scapoli et al., 2010). miR-146b seems to be also overexpressed in some prostate and colorectal cancers (Kanaan et al., 2012).
  
  
Entity Immunity
Note Innate immunity and inflammation play an important role in cancer development and it is therefore noteworthy to mention that the miR-146 family is involved in these mechanisms of cell protection. Even if more evidence has been gathered in the case of the former, both miR-146a and miR-146b control Toll-like receptor and cytokine signaling pathways. miR-146b is predicted to bind the 3'UTR of the IL-1 receptor-associated kinase 1 and TNF receptor-associated factor 6 transcripts. The expression of MIR146B is regulated by NF-κB (Taganov et al., 2006).
  

Bibliography

MicroRNA expression profile helps to distinguish benign nodules from papillary thyroid carcinomas starting from cells of fine-needle aspiration.
Agretti P, Ferrarini E, Rago T, Candelieri A, De Marco G, Dimida A, Niccolai F, Molinaro A, Di Coscio G, Pinchera A, Vitti P, Tonacchera M.
Eur J Endocrinol. 2012 Sep;167(3):393-400. doi: 10.1530/EJE-12-0400. Epub 2012 Jun 22.
PMID 22728346
 
MicroRNA profiles of healthy basal and luminal mammary epithelial cells are distinct and reflected in different breast cancer subtypes.
Bockmeyer CL, Christgen M, Muller M, Fischer S, Ahrens P, Langer F, Kreipe H, Lehmann U.
Breast Cancer Res Treat. 2011 Dec;130(3):735-45. doi: 10.1007/s10549-010-1303-3. Epub 2011 Mar 17.
PMID 21409395
 
MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma.
Chen YT, Kitabayashi N, Zhou XK, Fahey TJ 3rd, Scognamiglio T.
Mod Pathol. 2008 Sep;21(9):1139-46. doi: 10.1038/modpathol.2008.105. Epub 2008 Jun 27.
PMID 18587330
 
miR-146b is highly expressed in adult papillary thyroid carcinomas with high risk features including extrathyroidal invasion and the BRAF(V600E) mutation.
Chou CK, Chen RF, Chou FF, Chang HW, Chen YJ, Lee YF, Yang KD, Cheng JT, Huang CC, Liu RT.
Thyroid. 2010 May;20(5):489-94. doi: 10.1089/thy.2009.0027.
PMID 20406109
 
Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers.
Garcia AI, Buisson M, Bertrand P, Rimokh R, Rouleau E, Lopez BS, Lidereau R, Mikaelian I, Mazoyer S.
EMBO Mol Med. 2011 May;3(5):279-90. doi: 10.1002/emmm.201100136. Epub 2011 Apr 5.
PMID 21472990
 
MicroRNA miR-146b-5p regulates signal transduction of TGF-beta by repressing SMAD4 in thyroid cancer.
Geraldo MV, Yamashita AS, Kimura ET.
Oncogene. 2012 Apr 12;31(15):1910-22. doi: 10.1038/onc.2011.381. Epub 2011 Aug 29.
PMID 21874046
 
Circulating micro-RNA expression profiles in early stage nonsmall cell lung cancer.
Heegaard NH, Schetter AJ, Welsh JA, Yoneda M, Bowman ED, Harris CC.
Int J Cancer. 2012 Mar 15;130(6):1378-86. doi: 10.1002/ijc.26153. Epub 2011 Aug 26.
PMID 21544802
 
Microrna profiling analysis of differences between the melanoma of young adults and older adults.
Jukic DM, Rao UN, Kelly L, Skaf JS, Drogowski LM, Kirkwood JM, Panelli MC.
J Transl Med. 2010 Mar 19;8:27. doi: 10.1186/1479-5876-8-27.
PMID 20302635
 
Differential microRNA expression tracks neoplastic progression in inflammatory bowel disease-associated colorectal cancer.
Kanaan Z, Rai SN, Eichenberger MR, Barnes C, Dworkin AM, Weller C, Cohen E, Roberts H, Keskey B, Petras RE, Crawford NP, Galandiuk S.
Hum Mutat. 2012 Mar;33(3):551-60. doi: 10.1002/humu.22021.
PMID 22241525
 
Can the microRNA signature distinguish between thyroid tumors of uncertain malignant potential and other well-differentiated tumors of the thyroid gland?
Lassalle S, Hofman V, Ilie M, Bonnetaud C, Puissegur MP, Brest P, Loubatier C, Guevara N, Bordone O, Cardinaud B, Lebrigand K, Rios G, Santini J, Franc B, Mari B, Al Ghuzlan A, Vielh P, Barbry P, Hofman P.
Endocr Relat Cancer. 2011 Sep 13;18(5):579-94. doi: 10.1530/ERC-10-0283. Print 2011 Oct.
PMID 21778212
 
MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility.
Nikiforova MN, Tseng GC, Steward D, Diorio D, Nikiforov YE.
J Clin Endocrinol Metab. 2008 May;93(5):1600-8. doi: 10.1210/jc.2007-2696. Epub 2008 Feb 12.
PMID 18270258
 
Overexpression of the lung cancer-prognostic miR-146b microRNAs has a minimal and negative effect on the malignant phenotype of A549 lung cancer cells.
Patnaik SK, Kannisto E, Mallick R, Yendamuri S.
PLoS One. 2011;6(7):e22379. doi: 10.1371/journal.pone.0022379. Epub 2011 Jul 18.
PMID 21789255
 
Microrna expression profile in a large series of bladder tumors: Identification of a 3-mirna signature associated with aggressiveness of muscle-invasive bladder cancer.
Pignot G, Cizeron-Clairac G, Vacher S, Susini A, Tozlu S, Vieillefond A, Zerbib M, Lidereau R, Debre B, Amsellem-Ouazana D, Bieche I.
Int J Cancer. 2012 Nov 20. doi: 10.1002/ijc.27949. [Epub ahead of print]
PMID 23169479
 
Specific alterations of microRNA transcriptome and global network structure in colorectal carcinoma after cetuximab treatment.
Ragusa M, Majorana A, Statello L, Maugeri M, Salito L, Barbagallo D, Guglielmino MR, Duro LR, Angelica R, Caltabiano R, Biondi A, Di Vita M, Privitera G, Scalia M, Cappellani A, Vasquez E, Lanzafame S, Basile F, Di Pietro C, Purrello M.
Mol Cancer Ther. 2010 Dec;9(12):3396-409. doi: 10.1158/1535-7163.MCT-10-0137. Epub 2010 Sep 29.
PMID 20881268
 
MicroRNA classifiers for predicting prognosis of squamous cell lung cancer.
Raponi M, Dossey L, Jatkoe T, Wu X, Chen G, Fan H, Beer DG.
Cancer Res. 2009 Jul 15;69(14):5776-83. doi: 10.1158/0008-5472.CAN-09-0587. Epub 2009 Jul 7.
PMID 19584273
 
MicroRNA expression profiling of oral carcinoma identifies new markers of tumor progression.
Scapoli L, Palmieri A, Lo Muzio L, Pezzetti F, Rubini C, Girardi A, Farinella F, Mazzotta M, Carinci F.
Int J Immunopathol Pharmacol. 2010 Oct-Dec;23(4):1229-34.
PMID 21244772
 
MicroRNA signature in thyroid fine needle aspiration cytology applied to "atypia of undetermined significance" cases.
Shen R, Liyanarachchi S, Li W, Wakely PE Jr, Saji M, Huang J, Nagy R, Farrell T, Ringel MD, de la Chapelle A, Kloos RT, He H.
Thyroid. 2012 Jan;22(1):9-16. doi: 10.1089/thy.2011.0081. Epub 2011 Dec 2.
PMID 22136206
 
NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses.
Taganov KD, Boldin MP, Chang KJ, Baltimore D.
Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12481-6. Epub 2006 Aug 2.
PMID 16885212
 
microRNA-146b inhibits glioma cell migration and invasion by targeting MMPs.
Xia H, Qi Y, Ng SS, Chen X, Li D, Chen S, Ge R, Jiang S, Li G, Chen Y, He ML, Kung HF, Lai L, Lin MC.
Brain Res. 2009 May 7;1269:158-65. doi: 10.1016/j.brainres.2009.02.037. Epub 2009 Mar 3.
PMID 19265686
 
MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma.
Yip L, Kelly L, Shuai Y, Armstrong MJ, Nikiforov YE, Carty SE, Nikiforova MN.
Ann Surg Oncol. 2011 Jul;18(7):2035-41. doi: 10.1245/s10434-011-1733-0. Epub 2011 May 3.
PMID 21537871
 
microRNA and inflammatory gene expression as prognostic marker for overall survival in esophageal squamous cell carcinoma.
Zhao Y, Schetter AJ, Yang GB, Nguyen G, Mathe EA, Li P, Cai H, Yu L, Liu F, Hang D, Yang H, Wang XW, Ke Y, Harris CC.
Int J Cancer. 2012 Nov 23. doi: 10.1002/ijc.27954. [Epub ahead of print]
PMID 23175214
 

Citation

This paper should be referenced as such :
Garcia, A ; Mazoyer, S
MIR146B (microRNA 146b)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(5):337-340.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/MIR146BID50855ch10q24.html


External links

Nomenclature
HGNC (Hugo)MIR146B   32079
Cards
AtlasMIR146BID50855ch10q24
Entrez_Gene (NCBI)MIR146B  574447  microRNA 146b
AliasesMIRN146B; miRNA146B; mir-146b
GeneCards (Weizmann)MIR146B
Ensembl hg19 (Hinxton) [Gene_View]
Ensembl hg38 (Hinxton) [Gene_View]  chr10:102436512-102436584 [Contig_View]  MIR146B [Vega]
TCGA cBioPortalMIR146B
AceView (NCBI)MIR146B
Genatlas (Paris)MIR146B
WikiGenes574447
SOURCE (Princeton)MIR146B
Genetics Home Reference (NIH)MIR146B
miRBaseMIR146B
dbDEMCMIR146B
Genomic and cartography
GoldenPath hg38 (UCSC)MIR146B  -     chr10:102436512-102436584 +  10q24.32   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MIR146B  -     10q24.32   [Description]    (hg19-Feb_2009)
EnsemblMIR146B - 10q24.32 [CytoView hg19]  MIR146B - 10q24.32 [CytoView hg38]
Mapping of homologs : NCBIMIR146B [Mapview hg19]  MIR146B [Mapview hg38]
OMIM610567   
Gene and transcription
Genbank (Entrez)AY882276 LM609460
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)MIR146B
Gene ExpressionMIR146B [ NCBI-GEO ]   MIR146B [ EBI - ARRAY_EXPRESS ]   MIR146B [ SEEK ]   MIR146B [ MEM ]
Gene Expression Viewer (FireBrowse)MIR146B [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)574447
GTEX Portal (Tissue expression)MIR146B
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)MIR146B
DMDM Disease mutations574447
Blocks (Seattle)MIR146B
Protein Interaction databases
BioGRIDMIR146B
STRING (EMBL)MIR146B
ZODIACMIR146B
Ontologies - Pathways
Huge Navigator MIR146B [HugePedia]
snp3D : Map Gene to Disease574447
BioCentury BCIQMIR146B
ClinGenMIR146B
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD574447
Chemical/Pharm GKB GenePA164722498
Clinical trialMIR146B
Miscellaneous
canSAR (ICR)MIR146B (select the gene name)
Probes
Litterature
PubMed60 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMIR146B
EVEXMIR146B
GoPubMedMIR146B
iHOPMIR146B
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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