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MicroRNA 21
Symbols MIR21 ; MIRN21; hsa-mir-21; miR-21; miRNA21
External IDs OMIM611020 GeneCards: MIR21 Gene
Species Human Mouse
Entrez 406991 387140
Ensembl ENSG00000199004 ENSMUSG00000065455
UniProt n/a n/a
RefSeq (mRNA) NR_029493 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 precursor of miR-21(pre-miR-21) resides between nucleotides 2445 and 2516 of pri-miR-21.

Mature miR-21[edit]

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.


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[edit]


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[edit]

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]


  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. 
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  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. 
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  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[edit]

  • Cardin, S; Guasch, E; Luo, X; Naud, P; Le Quang, K; Shi, Y; Tardif, JC; Comtois, P; Nattel, S (October 2012). "Role for MicroRNA-21 in atrial profibrillatory fibrotic remodeling associated with experimental postinfarction heart failure.". Circulation. Arrhythmia and electrophysiology 5 (5): 1027–35. doi:10.1161/CIRCEP.112.973214. PMID 22923342. 
  • Zhong, Z; Dong, Z; Yang, L; Gong, Z (October 2012). "miR-21 induces cell cycle at S phase and modulates cell proliferation by down-regulating hMSH2 in lung cancer.". Journal of cancer research and clinical oncology 138 (10): 1781–8. doi:10.1007/s00432-012-1287-y. PMID 22806311. 

External links[edit]