MIRN21

Last updated
MIR21
Identifiers
Aliases MIR21 , MIRN21, hsa-mir-21, miR-21, miRNA21, microRNA 21, MIRN21 microRNA, human
External IDs OMIM: 611020 GeneCards: MIR21
Orthologs
SpeciesHumanMouse
Entrez

406991

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Ensembl

ENSG00000284190

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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

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

Contents

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]

Related Research Articles

The Let-7 microRNA precursor was identified from a study of developmental timing in C. elegans, and was later shown to be part of a much larger class of non-coding RNAs termed microRNAs. miR-98 microRNA precursor from human is a let-7 family member. Let-7 miRNAs have now been predicted or experimentally confirmed in a wide range of species (MIPF0000002). miRNAs are initially transcribed in long transcripts called primary miRNAs (pri-miRNAs), which are processed in the nucleus by Drosha and Pasha to hairpin structures of about 70 nucleotide. These precursors (pre-miRNAs) are exported to the cytoplasm by exportin5, where they are subsequently processed by the enzyme Dicer to a ~22 nucleotide mature miRNA. The involvement of Dicer in miRNA processing demonstrates a relationship with the phenomenon of RNA interference.

mir-129 microRNA precursor family

The miR-129 microRNA precursor is a small non-coding RNA molecule that regulates gene expression. This microRNA was first experimentally characterised in mouse and homologues have since been discovered in several other species, such as humans, rats and zebrafish. The mature sequence is excised by the Dicer enzyme from the 5' arm of the hairpin. It was elucidated by Calin et al. that miR-129-1 is located in a fragile site region of the human genome near a specific site, FRA7H in chromosome 7q32, which is a site commonly deleted in many cancers. miR-129-2 is located in 11p11.2.

mir-15 microRNA precursor family

The miR-15 microRNA precursor family is made up of small non-coding RNA genes that regulate gene expression. The family includes the related mir-15a and mir-15b sequences, as well as miR-16-1, miR-16-2, miR-195 and miR-497. These six highly conserved miRNAs are clustered on three separate chromosomes. In humans miR-15a and miR-16 are clustered within 0.5 kilobases at chromosome position 13q14. This region has been found to be the most commonly affected in chronic lymphocytic leukaemia (CLL), with deletions of the entire region in more than half of cases. Both miR-15a and miR-16 are thus frequently deleted or down-regulated in CLL samples with 13q14 deletions; occurring in more than two thirds of CLL cases. The expression of miR-15a is associated with survival in triple negative breast cancer.

mir-16 microRNA precursor family

The miR-16 microRNA precursor family is a group of related small non-coding RNA genes that regulates gene expression. miR-16, miR-15, mir-195 and miR-497 are related microRNA precursor sequences from the mir-15 gene family. This microRNA family appears to be vertebrate specific and its members have been predicted or experimentally validated in a wide range of vertebrate species.

mir-181 microRNA precursor

In molecular biology miR-181 microRNA precursor is a small non-coding RNA molecule. MicroRNAs (miRNAs) are transcribed as ~70 nucleotide precursors and subsequently processed by the RNase-III type enzyme Dicer to give a ~22 nucleotide mature product. In this case the mature sequence comes from the 5' arm of the precursor. They target and modulate protein expression by inhibiting translation and / or inducing degradation of target messenger RNAs. This new class of genes has recently been shown to play a central role in malignant transformation. miRNA are downregulated in many tumors and thus appear to function as tumor suppressor genes. The mature products miR-181a, miR-181b, miR-181c or miR-181d are thought to have regulatory roles at posttranscriptional level, through complementarity to target mRNAs. miR-181 which has been predicted or experimentally confirmed in a wide number of vertebrate species as rat, zebrafish, and in the pufferfish.

mir-19 microRNA precursor family

There are 89 known sequences today in the microRNA 19 (miR-19) family but it will change quickly. They are found in a large number of vertebrate species. The miR-19 microRNA precursor is a small non-coding RNA molecule that regulates gene expression. Within the human and mouse genome there are three copies of this microRNA that are processed from multiple predicted precursor hairpins:

mir-1 microRNA precursor family

The miR-1 microRNA precursor is a small micro RNA that regulates its target protein's expression in the cell. microRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give products at ~22 nucleotides. In this case the mature sequence comes from the 3' arm of the precursor. The mature products are thought to have regulatory roles through complementarity to mRNA. In humans there are two distinct microRNAs that share an identical mature sequence, and these are called miR-1-1 and miR-1-2.

The miR-34 microRNA precursor family are non-coding RNA molecules that, in mammals, give rise to three major mature miRNAs. The miR-34 family members were discovered computationally and later verified experimentally. The precursor miRNA stem-loop is processed in the cytoplasm of the cell, with the predominant miR-34 mature sequence excised from the 5' arm of the hairpin.

<span class="mw-page-title-main">TUSC2</span>

Tumor suppressor candidate 2 is a protein that in humans is encoded by the TUSC2 gene.

An oncomir is a microRNA (miRNA) that is associated with cancer. MicroRNAs are short RNA molecules about 22 nucleotides in length. Essentially, miRNAs specifically target certain messenger RNAs (mRNAs) to prevent them from coding for a specific protein. The dysregulation of certain microRNAs (oncomirs) has been associated with specific cancer forming (oncogenic) events. Many different oncomirs have been identified in numerous types of human cancers.

miR-137

In molecular biology, miR-137 is a short non-coding RNA molecule that functions to regulate the expression levels of other genes by various mechanisms. miR-137 is located on human chromosome 1p22 and has been implicated to act as a tumor suppressor in several cancer types including colorectal cancer, squamous cell carcinoma and melanoma via cell cycle control.

mir-143

In molecular biology mir-143 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. mir–143 is highly conserved in vertebrates. mir-143 is thought be involved in cardiac morphogenesis but has also been implicated in cancer.

mir-145

In molecular biology, mir-145 microRNA is a short RNA molecule that in humans is encoded by the MIR145 gene. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

mir-205

In molecular biology miR-205 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. They are involved in numerous cellular processes, including development, proliferation, and apoptosis. Currently, it is believed that miRNAs elicit their effect by silencing the expression of target genes.

mir-31

miR-31 has been characterised as a tumour suppressor miRNA, with its levels varying in breast cancer cells according to the metastatic state of the tumour. From its typical abundance in healthy tissue is a moderate decrease in non-metastatic breast cancer cell lines, and levels are almost completely absent in mouse and human metastatic breast cancer cell lines. Mir-31-5p has also been observed upregulated in Zinc Deficient rats compared to normal in ESCC and in other types of cancers when using this animal model. There has also been observed a strong encapsulation of tumour cells expressing miR-31, as well as a reduced cell survival rate. miR-31's antimetastatic effects therefore make it a potential therapeutic target for breast cancer. However, these two papers were formally retracted by the authors in 2015.

mir-210 microRNA

In molecular biology mir-210 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

miR-138

miR-138 is a family of microRNA precursors found in animals, including humans. MicroRNAs are typically transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. The excised region or, mature product, of the miR-138 precursor is the microRNA mir-138.

In molecular biology mir-301 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

<span class="mw-page-title-main">MicroRNA 93</span> Non-coding RNA in the species Homo sapiens

MicroRNA 93 is a functional RNA and a microRNA that in humans is encoded by the MIR93 gene.

References

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  18. 1 2 3 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. Bibcode:2008Natur.456..980T. doi:10.1038/nature07511. PMID   19043405. S2CID   4333547.
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  23. 1 2 3 Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. (February 2006). "A microRNA expression signature of human solid tumors defines cancer gene targets". Proceedings of the National Academy of Sciences of the United States of America. 103 (7): 2257–61. Bibcode:2006PNAS..103.2257V. doi: 10.1073/pnas.0510565103 . PMC   1413718 . PMID   16461460.
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  28. ↑ Lánczky A, Nagy Á, Bottai G, Munkácsy G, Szabó A, Santarpia L, Győrffy B (December 2016). "miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients". Breast Cancer Research and Treatment. 160 (3): 439–446. doi:10.1007/s10549-016-4013-7. PMID   27744485. S2CID   11165696.
  29. ↑ Yau TO, Tang CM, Harriss EK, Dickins B, Polytarchou C (July 2019). "Faecal microRNAs as a non-invasive tool in the diagnosis of colonic adenomas and colorectal cancer: A meta-analysis". Scientific Reports. 9 (1): 9491. Bibcode:2019NatSR...9.9491Y. doi:10.1038/s41598-019-45570-9. PMC   6603164 . PMID   31263200.
  30. ↑ Grolmusz VK, Kövesdi A, Borka K, Igaz P, Patocs A (July 2018). "Prognostic relevance of proliferation-related miRNAs in pancreatic neuroendocrine neoplasms". European Journal of Endocrinology. 179 (4): EJE–18–0305. doi: 10.1530/EJE-18-0305 . PMID   30006373.
  31. ↑ Roy S, Khanna S, Hussain SR, Biswas S, Azad A, Rink C, et al. (April 2009). "MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue". Cardiovascular Research. 82 (1): 21–9. doi:10.1093/cvr/cvp015. PMC   2652741 . PMID   19147652.
  32. ↑ Patrick DM, Montgomery RL, Qi X, Obad S, Kauppinen S, Hill JA, et al. (November 2010). "Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice". The Journal of Clinical Investigation. 120 (11): 3912–6. doi:10.1172/JCI43604. PMC   2964990 . PMID   20978354.
  33. ↑ Dong S, Cheng Y, Yang J, Li J, Liu X, Wang X, et al. (October 2009). "MicroRNA expression signature and the role of microRNA-21 in the early phase of acute myocardial infarction". The Journal of Biological Chemistry. 284 (43): 29514–25. doi: 10.1074/jbc.M109.027896 . PMC   2785585 . PMID   19706597.
  34. ↑ Louwies T, Vuegen C, Panis LI, Cox B, Vrijens K, Nawrot TS, De Boever P (May 2016). "miRNA expression profiles and retinal blood vessel calibers are associated with short-term particulate matter air pollution exposure". Environmental Research. 147: 24–31. Bibcode:2016ER....147...24L. doi:10.1016/j.envres.2016.01.027. PMID   26836502.

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