mIRN21

microRNA 21 also known as hsa-mir-21 or miRNA21 is a mammalian microRNA that is encoded by the MIR21 gene.[3]

MIR21
Identifiers
AliasesMIR21, MIRN21, hsa-mir-21, miR-21, miRNA21, microRNA 21
External IDsOMIM: 611020 GeneCards: MIR21
Gene location (Human)
Chr.Chromosome 17 (human)[1]
Band17q23.1Start59,841,266 bp[1]
End59,841,337 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

406991

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Ensembl

ENSG00000284190

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UniProt

n/a

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RefSeq (mRNA)

n/a

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RefSeq (protein)

n/a

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Location (UCSC)Chr 17: 59.84 – 59.84 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

MIRN21 was one of the first mammalian microRNAs identified. The mature miR-21 sequence is strongly conserved throughout evolution. The human microRNA-21 gene is located on plus strand of chromosome 17q23.2 (55273409–55273480) within a coding gene TMEM49 (also called vacuole membrane protein). Despite being located in intronic regions of a coding gene in the direction of transcription, it has its own promoter regions and forms a ~3433-nt long primary transcript of miR-21 (known as pri-miR-21) which is independently transcribed. The stem–loop precursor of miR-21(pre-miR-21) resides between nucleotides 2445 and 2516 of pri-miR-21.

Mature miR-21

Pri-miR-21 is cut by the endonuclease Drosha in the nucleus to produce pre-miR-21, which is exported into the cytosol. This pre-miR-21 is then cut into a short RNA duplex by Dicer in the cytosol. Although abundance of both strands is equal by transcription, only one strand (miR-21) is selected for processing as mature microRNA based on the thermodynamic stability of each end of the duplex, while the other strand (designated with an asterisk; miR-21*) is generally degraded. Mature microRNA is then loaded into microRNA ribonucleoprotein complex RISC (RNA-induced silencing complex) and guided to target mRNAs with near perfect complementarily at 3'UTR.

Targets

A number of targets for microRNA-21 have been experimentally validated and most of them are tumor suppressors, Notable targets include:

Clinical significance

Cancer

miR-21 is one of the most frequently upregulated miRNAs in solid tumours, and its high levels were first described in B cell lymphomas. Overall, miR-21 is considered to be a typical 'onco-miR', which acts by inhibiting the expression of phosphatases, which limit the activity of signalling pathways such as AKT and MAPK. As most of the targets of miR-21 are tumor suppressors, miR-21 is associated with a wide variety of cancers including that of breast,[20] ovaries,[21] cervix,[22] colon,[12] lung,[23] liver,[13] brain,[24] esophagus,[25] prostate,[23] pancreas,[23] and thyroid.[26] A 2014 meta-analysis of 36 studies evaluated circulating miR-21 as a biomarker of various carcinomas, finding it has potential as a tool for early diagnosis.[27] miR-21 expression was associated with survival in 53 triple negative breast cancer patients.[28] miR-21 can also be detected in human faeces from colorectal cancer patients.[29] Additionally, it has been demonstrated as an independent prognostic factor in patients with pancreatic neuroendocrine neoplasms.[30]

Cardiac disease

miR-21 has been shown to play important role in development of heart disease. It is one of the microRNAs whose expression is increased in failing murine and human hearts.[18][31] Further, inhibition of microRNAs in mice using chemically modified and cholesterol-conjugated miRNA inhibitors (antagomirs) was shown to inhibit interstitial fibrosis and improve cardiac function in a pressure- overload cardiac disease mice model.[18] Surprisingly, miR-21 global knock-out mice did not show any overt phenotype when compared with wild type mice with respect to cardiac stress response. Similarly, short (8-nt) oligonucleotides designed to inhibit miR-21 could not inhibit cardiac hypertrophy or fibrosis.[32] In another study with a mouse model of acute myocardial infarction, miR-21 expression was found to be significantly lower in infarcted areas and overexpression of miR-21 in those mice via adenovirus-mediated gene transfer decreased myocardial infarct size.[33] miR-21 has been hypothesized to be an intermediary in the effects of air pollution that lead to endothelial dysfunction and eventually to cardiac disease. Expression of miR-21 is negatively associated with exposure to PM10 air pollution and may mediate its effect on small blood vessels.[34]

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References
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  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  18. Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, et al. (December 2008). "MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts". Nature. 456 (7224): 980–4. doi:10.1038/nature07511. PMID 19043405.
  19. Sayed D, Rane S, Lypowy J, He M, Chen IY, Vashistha H, et al. (August 2008). "MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths". Molecular Biology of the Cell. 19 (8): 3272–82. doi:10.1091/mbc.E08-02-0159. PMC 2488276. PMID 18508928.
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Further reading

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