MIR146B (microRNA 146b)

2012-12-01   Amandine Garcia , Sylvie Mazoyer 

CNRS UMR5286 Inserm U1052, Universite Lyon 1, Cancer Research Centre of Lyon, Centre Leon Berard, Lyon, France

Identity

HGNC
LOCATION
10q24.32
LOCUSID
ALIAS
MIRN146B,miRNA146B,mir-146b

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.
Atlas Image
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.

Proteins

Note

microRNAs arent translated into amino acids.

Implicated in

Entity name
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 3UTR 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 name
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 3UTR 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 name
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 name
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 name
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 3UTR 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

Pubmed IDLast YearTitleAuthors
227283462012MicroRNA expression profile helps to distinguish benign nodules from papillary thyroid carcinomas starting from cells of fine-needle aspiration.Agretti P et al
214093952011MicroRNA profiles of healthy basal and luminal mammary epithelial cells are distinct and reflected in different breast cancer subtypes.Bockmeyer CL et al
185873302008MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma.Chen YT et al
204061092010miR-146b is highly expressed in adult papillary thyroid carcinomas with high risk features including extrathyroidal invasion and the BRAF(V600E) mutation.Chou CK et al
214729902011Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers.Garcia AI et al
218740462012MicroRNA miR-146b-5p regulates signal transduction of TGF-β by repressing SMAD4 in thyroid cancer.Geraldo MV et al
215448022012Circulating micro-RNA expression profiles in early stage nonsmall cell lung cancer.Heegaard NH et al
203026352010Microrna profiling analysis of differences between the melanoma of young adults and older adults.Jukic DM et al
222415252012Differential microRNA expression tracks neoplastic progression in inflammatory bowel disease-associated colorectal cancer.Kanaan Z et al
217782122011Can the microRNA signature distinguish between thyroid tumors of uncertain malignant potential and other well-differentiated tumors of the thyroid gland?Lassalle S et al
182702582008MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility.Nikiforova MN et al
217892552011Overexpression 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 et al
231694792013microRNA 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 et al
208812682010Specific alterations of microRNA transcriptome and global network structure in colorectal carcinoma after cetuximab treatment.Ragusa M et al
195842732009MicroRNA classifiers for predicting prognosis of squamous cell lung cancer.Raponi M et al
212447722010MicroRNA expression profiling of oral carcinoma identifies new markers of tumor progression.Scapoli L et al
221362062012MicroRNA signature in thyroid fine needle aspiration cytology applied to "atypia of undetermined significance" cases.Shen R et al
168852122006NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses.Taganov KD et al
192656862009microRNA-146b inhibits glioma cell migration and invasion by targeting MMPs.Xia H et al
215378712011MicroRNA signature distinguishes the degree of aggressiveness of papillary thyroid carcinoma.Yip L et al
231752142013microRNA and inflammatory gene expression as prognostic marker for overall survival in esophageal squamous cell carcinoma.Zhao Y et al

Other Information

Locus ID:

NCBI: 574447
MIM: 610567
HGNC: 32079
Ensembl: ENSG00000202569
miRBase:

Variants:

dbSNP: 574447
ClinVar: 574447
TCGA: ENSG00000202569
COSMIC: MIR146B

RNA/Proteins

References

Pubmed IDYearTitleCitations
185044312008Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells.227
214729902011Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers.96
237984302013Negative regulation of Toll-like receptor 4 signaling by IL-10-dependent microRNA-146b.91
192656862009microRNA-146b inhibits glioma cell migration and invasion by targeting MMPs.76
204061092010miR-146b is highly expressed in adult papillary thyroid carcinomas with high risk features including extrathyroidal invasion and the BRAF(V600E) mutation.68
244731962014STAT3 induction of miR-146b forms a feedback loop to inhibit the NF-κB to IL-6 signaling axis and STAT3-driven cancer phenotypes.56
237966922013miR-146b-5p inhibits glioma migration and invasion by targeting MMP16.46
235929102013Differential regulation of microRNA-146a and microRNA-146b-5p in human retinal pigment epithelial cells by interleukin-1β, tumor necrosis factor-α, and interferon-γ.41
263201762015miR-146b-5p functions as a tumor suppressor by targeting TRAF6 and predicts the prognosis of human gliomas.35
284049232017Down-regulation of miR-146b-5p by long noncoding RNA MALAT1 in hepatocellular carcinoma promotes cancer growth and metastasis.35

Citation

Amandine Garcia ; Sylvie Mazoyer

MIR146B (microRNA 146b)

Atlas Genet Cytogenet Oncol Haematol. 2012-12-01

Online version: http://atlasgeneticsoncology.org/gene/50855/mir146b