MIR146A

Summary

MIR146A (microRNA 146a, HGNC:31533) is a microRNA gene on chromosome 5q33.3.

microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. Some of the targets of the encoded miRNA are the transcripts for tumor necrosis factor, interleukin 1 receptor-associated kinase 1, interleukin 1-beta, TNF receptor-associated factor 6, and complement factor H. The RefSeq represents the predicted microRNA stem-loop.

Source: NCBI Gene 406938 — RefSeq curated summary.

At a glance

• Gene type: non-coding (miRNA) — no protein product; not a drug target. Variant/disease associations are omitted (they would be positional, from an overlapping protein-coding gene).

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31533
Approved symbol	MIR146A
Name	microRNA 146a
Location	5q33.3
Locus type	RNA, micro
Status	Approved
Aliases	hsa-mir-146, hsa-mir-146a
Ensembl gene	ENSG00000283733
Ensembl biotype	miRNA
OMIM	610566
Entrez	406938
RNAcentral	URS000075D8A0 — miRNA, 99 nt, 1 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 miRNA

ENST00000385201

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000385201 — 1 exons

Exon	Start	End
ENSE00001500207	160485352	160485450

Expression profiles

Bgee: expression breadth broad, 12 present calls, max score 97.67.

Top tissues by expression

12 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
renal glomerulus	UBERON:0000074	97.67	gold quality
prostate gland	UBERON:0002367	76.40	gold quality
gastrocnemius	UBERON:0001388	71.26	gold quality
tibial artery	UBERON:0007610	69.80	gold quality
left lobe of thyroid gland	UBERON:0001120	65.36	gold quality
blood	UBERON:0000178	65.24	gold quality
skin of abdomen	UBERON:0001416	61.33	gold quality
spleen	UBERON:0002106	61.08	gold quality
omental fat pad	UBERON:0010414	57.59	gold quality
testis	UBERON:0000473	57.40	gold quality
small intestine Peyer’s patch	UBERON:0003454	54.48	gold quality
nucleus accumbens	UBERON:0001882	53.98	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, NFKB

Literature-anchored findings (GeneRIF, showing 40)

• miR-146 is 19-fold upregulated in papillary thyroid carcinoma; its function is impaired by SNP within its target cKIT (PMID:16365291)
• miR-146a was significantly overexpressed in psoriatic lesional skin but not in atopic eczema lesions when compared with healthy skin. CD4+CD25(high) regulatory T cells, monocyte-derived dendritic cells and mast cells expressed miR-146a at a high level. (PMID:17622355)
• LMP1 dysregulates the expression of several cellular miRNAs, including the most highly regulated of these, miR-146a. (PMID:18057241)
• synovial fibroblasts showed increased expression of miRNA miR-155 (microRNA 155) and miR-146a (microRNA 146a) in Rheumatoid Arthritis (PMID:18383392)
• studies indicate that rapid increase in miRNA-146a expression provides a novel mechanism for the negative regulation of severe inflammation during the innate immune response (PMID:18390754)
• a pre-miR-146a single nucleotide polymorphism decreases mature miR expression and predisposes to papillary thyroid carcinoma (PMID:18474871)
• Data indicate that megakaryopoiesis is controlled by a cascade pathway, in which PLZF suppresses miR-146a transcription and thereby activates CXCR4 translation. (PMID:18568019)
• breast/ovarian cancer patients with variant C allele miR-146a may have high levels of mature miR-146 and that these variants predispose them to an earlier age of onset of familial breast and ovarian cancers. (PMID:18660546)
• data suggest that the G > C polymorphism in miR-146a precursor may result in important phenotypic traits that is associated with risk of hepatocellular carcinoma (PMID:18711148)
• miR-146a expression is increased but unable to properly function, leading to prolonged tumor necrosis factor-alpha production in patients with rheumatoid arthritis. (PMID:18759964)
• NF-kappaB-sensitive miRNA-146a-mediated modulation of complement factor H gene expression may in part regulate an inflammatory response in Alzheimer disease brain (PMID:18801740)
• These data demonstrate that cellular microRNAs are deregulated in HTLV-1-transformed T cells. In the case of miR-146a, this could be directly attributed to HTLV’s oncoprotein Tax. (PMID:19014482)
• GC heterozygotes of miR-146a differ from both GG and CC homozygotes by producing 3 mature microRNAs: 1 from the leading strand (miR-146a), and 2 from the passenger strand (miR-146a*G and miR-146a*C), each with its distinct set of target genes. (PMID:19164563)
• TaqMan analysis of paired tumor/normal samples revealed 1.5- to 2.6-fold overexpression of polymorphic miR-146a* in 7 of 8 tumors compared with the unaffected part of the same gland (PMID:19164563)
• miRNA-146a was up-regulated in human bronchial epithelial cells in response to stimulation by cytokines. (PMID:19167348)
• Results support the recent notion that modulating the levels of miR-146a or miR-146b could have a therapeutic potential to suppress breast cancer metastasis. (PMID:19190326)
• The microRNA miR-146a is a negative regulator of the type I interferon pathway (PMID:19333922)
• miR-146 is intensely expressed in low-grade osteoarthritis cartilage and that its expression is induced by stimulation of IL-1beta (PMID:19333945)
• GC heterozygotes of pre-miR-146a present higher activity of NF-kappa-B and lower potential of inhibition of this pathway in thyroid tissue (PMID:19411858)
• miRNA-146a is regulated by NF-kB in the human brain and is up-regulated in Alzheimer’s disease. In primary human brain cells, oxidative stress (Al3+ plus Fe2+) causes up-regulation of miRNA-146a, which leads to down-regulation of complement factor H. (PMID:19540598)
• Data demonstrate that miR-146a is critical for the in vitro monocytic cell-based endotoxin tolerance. (PMID:19840932)
• lowered expression in myelodysplastic syndrome with deletion of the long arm of chromosome 5 (del(5q)) (PMID:19898489)
• The natural genetic variation in pre-miR-146a affects the amount of mature miR-146a, contributes to the genetic predisposition to prostatic cancer. (PMID:19902466)
• Inhibition of miR-146a expression failed to alter the cell cycle distribution or angiogenesis induced by PMA treatment. (PMID:19944095)
• Studies indicate that several miRNAs are shown to be part of negative feedback loops (miR-155, miR-146, miR-9) in innate immune responses, in which they may limit excessive inflammation. (PMID:19954362)
• miR-146a enforced expression impairs both activator protein 1 (AP-1) activity and interleukin-2 (IL-2) production induced by TCR engagement, thus suggesting a role of this miRNA in the modulation of adaptive immunity. (PMID:19965651)
• SNP in NLRP3 and miR-146a were not associated with the susceptibility to Chlamydia trachomatis infections. (PMID:20011700)
• overexpression of miR-146a enhanced the growth of an HTLV-1-infected T-cell line. (PMID:20017139)
• Replicative senescence (RS) in human trabecular meshwork (HTM) cells was associated with changes in miRNA expression that could influence the senescent phenotype. (PMID:20053980)
• miR-146a promotes the differentiation in periodontal ligament cells through the down-regulation of NF-kappaB signaling. (PMID:20110513)
• miR-146a suppresses invasion of pancreatic cancer cells. (PMID:20124483)
• CCL8/MCP-2 is a target for mir-146a in HIV-1 infected microglia, as overexpression of mir-146a prevented HIV-induced secretion of MCP-2 chemokine (PMID:20181935)
• Serum miR-146a and miR-223 might serve as new biomarkers for sepsis with high specificity and sensitivity. (PMID:20188071)
• miR-146a may be a novel regulatory factor in Th1 differentiation and a new therapeutic target for atherosclerosis (PMID:20195282)
• This study demonstrated an upregulation of miR-146a with prominent expression in astrocytes during epileptogenesis in a rat model of temporal lobe epilepsy as well as in human temporal lobe epilepsy. (PMID:20214679)
• High constitutive miR-146a levels are induced by microenvironmental signals in the epidermis and might render Langerhans cells less susceptible to inappropriate activation by commensal bacterial TLR2 triggers at body surfaces. (PMID:20375304)
• manipulation of miR-146a expression may represent a potential new therapy for several human diseases (PMID:20384865)
• These results suggest that Bisphenol A(BPA) can alter miRNA expression in placental cells, a potentially novel mode of BPA toxicity. (PMID:20417706)
• Regulation of TBP by miR-146a may contribute to Huntington disease pathogenesis. (PMID:20451497)
• Marginally significant difference was observed in distribution of IRAK1 rs1059703 genotypes between patients with psoriatic arthritis and controls (P = 0.058), but no difference was observed in miRNA-146a rs2910164 distribution (P = 0.394). (PMID:20500689)

Cross-species orthologs

0 orthologs

Protein

Non-coding RNA — no protein product; not a drug target.

Function

No curated pathway, Gene-Ontology, or interaction data.

Disease & clinical

No curated disease, variant, or cancer-driver associations.

Drugs & pharmacology

No drug or pharmacology data — not an established drug target.