mIRN21

MicroRNA 21
Identifiers
Symbols MIR21; MIRN21; hsa-mir-21; miR-21; miRNA21
External IDs OMIM: 611020 GeneCards: MIR21 Gene
Orthologs
Species Human Mouse
Entrez 406991 387140
Ensembl ENSG00000199004 ENSMUSG00000065455
UniProt n/a n/a
RefSeq (mRNA) NR_029493.1 NR_029738.1
RefSeq (protein) n/a n/a
Location (UCSC) Chr 17:
57.92 – 57.92 Mb		 Chr 11:
-86.4 – -86.4 Mb
PubMed search [1] [2]

microRNA 21 also known as hsa-mir-21 or miRNA21 is a mammalian microRNA that is encoded by the MIR21 gene.[1]

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 recursor of miR-21(pre-miR-21) resides between nucleotides 2445 and 2516 of pri-miR-21.

Contents

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 in to 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 complimentarily 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 PTEN,[2] PDCD4,[3] Tropomyosin,[4] Sprouty 1,[5] Sprouty 2,[6] Bcl2,[7] RECK,[8] IL-12p35,[9] JAG1,[10] HNRPK,[4] BTG2,[11] TGFBRII,[12] TAp63,[4] P12/CDK2AP1,[13] MEF2C,[14] ANP32A, SMARCA4,[15] RhoB,[16] and hMSH2.[17]

Clinical significance

Cancer

MiR-21 is one of the first microRNA to be described as an oncomir. As most of the targets of miR-21 are tumour suppressors, miR-21 is associated with a wide variety of cancers including that of breast,[18] ovaries,[19] cervix,[20] colon,[3] lung,[21] liver,[2] brain,[22] oesophagus,[23] prostate,[21] pancreas,[21] and thyroid.[24]

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.[5][25] 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.[5] 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.[26] 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.[27]

References

  1. ^ Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (October 2001). "Identification of novel genes coding for small expressed RNAs". Science 294 (5543): 853–8. doi:10.1126/science.1064921. PMID 11679670. 
  2. ^ 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): 647–58. doi:10.1053/j.gastro.2007.05.022. PMID 17681183. 
  3. ^ a b Asangani IA, Rasheed SA, Nikolova DA, et al. (April 2008). "MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer". Oncogene 27 (15): 2128–36. doi:10.1038/sj.onc.1210856. PMID 17968323. 
  4. ^ a b c Papagiannakopoulos T, Shapiro A, Kosik KS (October 2008). "MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells". Cancer Res. 68 (19): 8164–72. doi:10.1158/0008-5472.CAN-08-1305. PMID 18829576. 
  5. ^ a b c Thum T, Gross C, Fiedler J, 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. 
  6. ^ Sayed D, Rane S, Lypowy J, et al. (August 2008). "MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths". Mol. Biol. Cell 19 (8): 3272–82. doi:10.1091/mbc.E08-02-0159. PMC 2488276. PMID 18508928. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2488276. 
  7. ^ Wickramasinghe NS, Manavalan TT, Dougherty SM, Riggs KA, Li Y, Klinge CM (May 2009). "Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells". Nucleic Acids Res. 37 (8): 2584–95. doi:10.1093/nar/gkp117. PMC 2677875. PMID 19264808. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2677875. 
  8. ^ Gabriely G, Wurdinger T, Kesari S, et al. (September 2008). "MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators". Mol. Cell. Biol. 28 (17): 5369–80. doi:10.1128/MCB.00479-08. PMC 2519720. PMID 18591254. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2519720. 
  9. ^ Lu TX, Munitz A, Rothenberg ME (April 2009). "MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression". J. Immunol. 182 (8): 4994–5002. doi:10.4049/jimmunol.0803560. PMID 19342679. 
  10. ^ Hashimi ST, Fulcher JA, Chang MH, Gov L, Wang S, Lee B (July 2009). "MicroRNA profiling identifies miR-34a and miR-21 and their target genes JAG1 and WNT1 in the coordinate regulation of dendritic cell differentiation". Blood 114 (2): 404–14. doi:10.1182/blood-2008-09-179150. PMC 2927176. PMID 19398721. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2927176. 
  11. ^ Liu M, Wu H, Liu T, et al. (July 2009). "Regulation of the cell cycle gene, BTG2, by miR-21 in human laryngeal carcinoma". Cell Res. 19 (7): 828–37. doi:10.1038/cr.2009.72. PMID 19546886. 
  12. ^ 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): 3093–102. doi:10.1002/stem.235. PMID 19816956. 
  13. ^ Zheng J, Xue H, Wang T, et al. (March 2011). "miR-21 downregulates the tumor suppressor P12(CDK2AP1) and Stimulates Cell Proliferation and Invasion". J. Cell. Biochem. 112 (3): 872–80. doi:10.1002/jcb.22995. PMID 21328460. 
  14. ^ Yelamanchili SV, Chaudhuri AD, Chen LN, Xiong H, Fox HS (September 2010). "MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease". Cell Death Dis 1 (9): e77. doi:10.1038/cddis.2010.56. PMC 3002786. PMID 21170291. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3002786. 
  15. ^ Schramedei K, Mörbt N, Pfeifer G, et al. (February 2011). "MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4". Oncogene 30 (26). doi:10.1038/onc.2011.15. PMID 21317927. 
  16. ^ Sabatel C, Malvaux L, Bovy N, et al. (2011). Capogrossi, Maurizio. ed. "MicroRNA-21 Exhibits Antiangiogenic Function by Targeting RhoB Expression in Endothelial Cells". PLoS ONE 6 (2): e16979. doi:10.1371/journal.pone.0016979. PMC 3037403. PMID 21347332. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3037403. 
  17. ^ Valeri N, Gasparini P, Braconi C, et al. (December 2010). "MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2)". Proc. Natl. Acad. Sci. U.S.A. 107 (49): 21098–103. doi:10.1073/pnas.1015541107. PMC 3000294. PMID 21078976. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3000294. 
  18. ^ Iorio MV, Ferracin M, Liu CG, et al. (August 2005). "MicroRNA gene expression deregulation in human breast cancer". Cancer Res. 65 (16): 7065–70. doi:10.1158/0008-5472.CAN-05-1783. PMID 16103053. 
  19. ^ Iorio MV, Visone R, Di Leva G, et al. (September 2007). "MicroRNA signatures in human ovarian cancer". Cancer Res. 67 (18): 8699–707. doi:10.1158/0008-5472.CAN-07-1936. PMID 17875710. 
  20. ^ Lui WO, Pourmand N, Patterson BK, Fire A (July 2007). "Patterns of known and novel small RNAs in human cervical cancer". Cancer Res. 67 (13): 6031–43. doi:10.1158/0008-5472.CAN-06-0561. PMID 17616659. 
  21. ^ a b c Volinia S, Calin GA, Liu CG, et al. (February 2006). "A microRNA expression signature of human solid tumors defines cancer gene targets". Proc. Natl. Acad. Sci. U.S.A. 103 (7): 2257–61. doi:10.1073/pnas.0510565103. PMC 1413718. PMID 16461460. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1413718. 
  22. ^ Chan JA, Krichevsky AM, Kosik KS (July 2005). "MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells". Cancer Res. 65 (14): 6029–33. doi:10.1158/0008-5472.CAN-05-0137. PMID 16024602. 
  23. ^ Hu Y, Correa AM, Hoque A, et al. (January 2011). "Prognostic significance of differentially expressed miRNAs in esophageal cancer". Int. J. Cancer 128 (1): 132–43. doi:10.1002/ijc.25330. PMC 2937084. PMID 20309880. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2937084. 
  24. ^ Tetzlaff MT, Liu A, Xu X, et al. (2007). "Differential expression of miRNAs in papillary thyroid carcinoma compared to multinodular goiter using formalin fixed paraffin embedded tissues". Endocr. Pathol. 18 (3): 163–73. doi:10.1007/s12022-007-0023-7. PMID 18058265. 
  25. ^ Roy S, Khanna S, Hussain SR, et al. (April 2009). "MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue". Cardiovasc. Res. 82 (1): 21–9. doi:10.1093/cvr/cvp015. PMC 2652741. PMID 19147652. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2652741. 
  26. ^ Patrick DM, Montgomery RL, Qi X, et al. (November 2010). "Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice". J. Clin. Invest. 120 (11): 3912–6. doi:10.1172/JCI43604. PMC 2964990. PMID 20978354. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2964990. 
  27. ^ Dong S, Cheng Y, Yang J, et al. (October 2009). "MicroRNA expression signature and the role of microRNA-21 in the early phase of acute myocardial infarction". J. Biol. Chem. 284 (43): 29514–25. doi:10.1074/jbc.M109.027896. PMC 2785585. PMID 19706597. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2785585. 

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