mIRN21

MicroRNA 21
Identifiers
SymbolsMIR21 ; MIRN21; hsa-mir-21; miR-21; miRNA21
External IDsOMIM: 611020 GeneCards: MIR21 Gene
Orthologs
SpeciesHumanMouse
Entrez406991387140
EnsemblENSG00000199004ENSMUSG00000065455
UniProtn/an/a
RefSeq (mRNA)NR_029493NR_029738.1
RefSeq (protein)n/an/a
Location (UCSC)Chr 17:
57.92 – 57.92 Mb		Chr 11:
-86.4 – -86.4 Mb
PubMed search

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 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 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 tumor 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] esophagus,[23] prostate,[21] pancreas,[21] and thyroid.[24] A 2014 meta-analysis of 36 studies evaluated circulating miR-21 as a biomarker of various carinomas, finding it has potential as a tool for early diagnosis.[25]

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][26] 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.[27] 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.[28]

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. ↑ 2.0 2.1 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. ↑ 3.0 3.1 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. ↑ 4.0 4.1 4.2 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. ↑ 5.0 5.1 5.2 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.
  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.
  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.
  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.
  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.
  15. ↑ Schramedei K, Mörbt N, Pfeifer G et al. (February 2011). "MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4". Oncogene 30 (26): 2975–85. doi:10.1038/onc.2011.15. PMC 3134876. 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.
  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.
  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. ↑ 21.0 21.1 21.2 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.
  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.
  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. ↑ "Circulating microRNA-21 as a biomarker for the detection of various carcinomas: an updated meta-analysis based on 36 studies." 36. Dec 20, 2014. pp. 1973–81. doi:10.1007/s13277-014-2803-2. PMID 25527152.
  26. ↑ 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.
  27. ↑ 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.
  28. ↑ 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.

Further reading

External links