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mIRN21

From Wikipedia, the free encyclopedia

MIR21
Identifiers
AliasesMIR21, MIRN21, hsa-mir-21, miR-21, miRNA21, microRNA 21, MIRN21 microRNA, human
External IDsOMIM: 611020; GeneCards: MIR21; OMA:MIR21 - orthologs
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 Mbn/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]

Gene

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MIRN21 was one of the first mammalian microRNAs identified. The human microRNA-21 gene is located on the plus strand of chromosome 17q23.2 (55273409–55273480), within the coding gene TMEM49 (also known as vacuole membrane protein). Although it resides within the intronic region of this gene and shares the same direction of transcription, miR-21 has its own promoter regions and is independently transcribed. Its primary transcript (pri-miR-21) is approximately 3433 nucleotides in length. The precursor stem–loop structure of miR-21 (pre-miR-21) is located between nucleotides 2445 and 2516 of pri-miR-21.

Structure

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Pri-miR-21 is initially processed in the nucleus by the endonuclease Drosha, which cleaves it into the precursor form, pre-miR-21. This precursor is then exported into the cytosol, where it is further cleaved by the enzyme Dicer into a short RNA duplex. Although both strands are transcribed in equal abundance, only one strand—designated as mature miR-21—is selectively incorporated into the RNA-induced silencing complex (RISC), based on the thermodynamic stability of the duplex ends. The other strand, labeled miR-21*, is typically degraded. The mature miRNA then guides the RISC complex to target mRNAs, usually binding near-perfectly to sequences within the 3'UTR.

Function

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MicroRNA-21 is a highly conserved small noncoding RNA that plays a central role in regulating gene expression across a broad range of biological processes, including development, immune response, and cellular homeostasis.[4] It modulates immune system activity by regulating T cell effector functions and maintaining the balance between Th1 and Th2 responses.[5]

Targets

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

Clinical significance

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Cancer

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miR-21 is frequently overexpressed in a wide variety of human cancers and is classified as a prototypical onco-miR.[22][23][24] It promotes tumorigenesis, metastasis, and resistance to therapy by targeting a range of tumor suppressor genes and signaling pathways.[22][25] Dysregulation of miR-21 is also implicated in various non-cancerous diseases, including cardiovascular and inflammatory conditions, underscoring its broad role in human pathology.[4][22]

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 lymphoma,[26] breast,[27] ovaries,[28] cervix,[29] colon,[14] lung,[30] liver,[15] brain,[31] esophagus,[32] prostate,[30] pancreas,[30] and thyroid.[33] In 2010, it was develop the first-in class in vivo model where a non-coding RNA (including a microRNA) is able to create and maintain a tumor[26] in the first described onco-miRNA adicction.[34] 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.[35] miR-21 expression was associated with survival in 53 triple negative breast cancer patients.[36] miR-21 can also be detected in human faeces from colorectal cancer patients.[37] Additionally, it has been demonstrated as an independent prognostic factor in patients with pancreatic neuroendocrine neoplasms.[38]

Cardiac disease

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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.[20][39] 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.[20] 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.[40] 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.[41] 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.[42]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000284190 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (October 2001). "Identification of novel genes coding for small expressed RNAs". Science. 294 (5543). New York, N.Y.: 853–858. Bibcode:2001Sci...294..853L. doi:10.1126/science.1064921. hdl:11858/00-001M-0000-0012-F65F-2. PMID 11679670. S2CID 18101169.
  4. ^ a b Kumarswamy R, Volkmann I, Thum T (2011). "Regulation and function of miRNA-21 in health and disease". RNA Biology. 8 (5): 706–713. doi:10.4161/rna.8.5.16154. PMC 3256347. PMID 21712654.
  5. ^ Lu TX, Hartner J, Lim EJ, Fabry V, Mingler MK, Cole ET, et al. (September 2011). "MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-gamma pathway, Th1 polarization, and the severity of delayed-type hypersensitivity". Journal of Immunology. 187 (6). Baltimore, Md.: 3362–3373. doi:10.4049/jimmunol.1101235. PMC 3175642. PMID 21849676.
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  15. ^ a b Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T (August 2007). "MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer". Gastroenterology. 133 (2): 647–658. doi:10.1053/j.gastro.2007.05.022. PMC 4285346. PMID 17681183.
  16. ^ Gabriely G, Wurdinger T, Kesari S, Esau CC, Burchard J, Linsley PS, et al. (September 2008). "MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators". Molecular and Cellular Biology. 28 (17): 5369–5380. doi:10.1128/MCB.00479-08. PMC 2519720. PMID 18591254.
  17. ^ Sabatel C, Malvaux L, Bovy N, Deroanne C, Lambert V, Gonzalez ML, et al. (February 2011). "MicroRNA-21 exhibits antiangiogenic function by targeting RhoB expression in endothelial cells". PLOS ONE. 6 (2): e16979. Bibcode:2011PLoSO...616979S. doi:10.1371/journal.pone.0016979. PMC 3037403. PMID 21347332.
  18. ^ Schramedei K, Mörbt N, Pfeifer G, Läuter J, Rosolowski M, Tomm JM, et al. (June 2011). "MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4". Oncogene. 30 (26): 2975–2985. doi:10.1038/onc.2011.15. PMC 3134876. PMID 21317927.
  19. ^ Kim YJ, Hwang SJ, Bae YC, Jung JS (December 2009). "MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stem cells derived from human adipose tissue". Stem Cells. 27 (12). Dayton, Ohio: 3093–3102. doi:10.1002/stem.235. PMID 19816956. S2CID 32454261.
  20. ^ a b c 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): 980–984. Bibcode:2008Natur.456..980T. doi:10.1038/nature07511. PMID 19043405. S2CID 4333547.
  21. ^ 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): 3272–3282. doi:10.1091/mbc.E08-02-0159. PMC 2488276. PMID 18508928.
  22. ^ a b c Feng YH, Tsao CJ (October 2016). "Emerging role of microRNA-21 in cancer". Biomedical Reports. 5 (4): 395–402. doi:10.3892/br.2016.747. PMC 5038362. PMID 27699004.
  23. ^ Zhu W, Xu B (2014). "MicroRNA-21 identified as predictor of cancer outcome: a meta-analysis". PLOS ONE. 9 (8): e103373. Bibcode:2014PLoSO...9j3373Z. doi:10.1371/journal.pone.0103373. PMC 4123876. PMID 25098165.
  24. ^ Rhim J, Baek W, Seo Y, Kim JH (September 2022). "From Molecular Mechanisms to Therapeutics: Understanding MicroRNA-21 in Cancer". Cells. 11 (18): 2791. doi:10.3390/cells11182791. PMC 9497241. PMID 36139366.
  25. ^ Lao TD, Quang MT, Le TA (December 2021). "The Role of hsa-miR-21 and Its Target Genes Involved in Nasopharyngeal Carcinoma". Asian Pacific Journal of Cancer Prevention : APJCP. 22 (12): 4075–4083. doi:10.31557/APJCP.2021.22.12.4075. PMC 9080362. PMID 34967592.
  26. ^ a b Medina PP, Nolde M, Slack FJ (September 2010). "OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma". Nature. 467 (7311): 86–90. Bibcode:2010Natur.467...86M. doi:10.1038/nature09284. PMID 20693987.
  27. ^ Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. (August 2005). "MicroRNA gene expression deregulation in human breast cancer". Cancer Research. 65 (16): 7065–7070. doi:10.1158/0008-5472.CAN-05-1783. PMID 16103053.
  28. ^ Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, et al. (September 2007). "MicroRNA signatures in human ovarian cancer". Cancer Research. 67 (18): 8699–8707. doi:10.1158/0008-5472.CAN-07-1936. hdl:11577/3162525. PMID 17875710.
  29. ^ Lui WO, Pourmand N, Patterson BK, Fire A (July 2007). "Patterns of known and novel small RNAs in human cervical cancer". Cancer Research. 67 (13): 6031–6043. doi:10.1158/0008-5472.CAN-06-0561. PMID 17616659.
  30. ^ a b c 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): 2257–2261. Bibcode:2006PNAS..103.2257V. doi:10.1073/pnas.0510565103. PMC 1413718. PMID 16461460.
  31. ^ Chan JA, Krichevsky AM, Kosik KS (July 2005). "MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells". Cancer Research. 65 (14): 6029–6033. doi:10.1158/0008-5472.CAN-05-0137. PMID 16024602.
  32. ^ Hu Y, Correa AM, Hoque A, Guan B, Ye F, Huang J, et al. (January 2011). "Prognostic significance of differentially expressed miRNAs in esophageal cancer". International Journal of Cancer. 128 (1): 132–143. doi:10.1002/ijc.25330. PMC 2937084. PMID 20309880.
  33. ^ Tetzlaff MT, Liu A, Xu X, Master SR, Baldwin DA, Tobias JW, et al. (2007). "Differential expression of miRNAs in papillary thyroid carcinoma compared to multinodular goiter using formalin fixed paraffin embedded tissues". Endocrine Pathology. 18 (3): 163–173. doi:10.1007/s12022-007-0023-7. PMID 18058265. S2CID 40279671.
  34. ^ Dornan D, Settleman J (September 2010). "Cancer: miRNA addiction - depending on life's little things". Current Biology : CB. 20 (18): R812 – R813. Bibcode:2010CBio...20.R812D. doi:10.1016/j.cub.2010.08.040. PMID 20869610.
  35. ^ Wu K, Li L, Li S (March 2015). "Circulating microRNA-21 as a biomarker for the detection of various carcinomas: an updated meta-analysis based on 36 studies". Tumour Biology : The Journal of the International Society for Oncodevelopmental Biology and Medicine. 36 (3): 1973–1981. doi:10.1007/s13277-014-2803-2. PMID 25527152. S2CID 26060312.
  36. ^ Lánczky A, Nagy Á, Bottai G, Munkácsy G, Szabó A, Santarpia L, et al. (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.
  37. ^ 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.
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  42. ^ Louwies T, Vuegen C, Panis LI, Cox B, Vrijens K, Nawrot TS, et al. (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.

Further reading

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