Mir-1 microRNA precursor family explained

miR-1
Symbol:	mir-1
Rfam:	RF00103
Mirbase:	MI0000651
Mirbase Family:	MIPF0000038
Rna Type:	Gene; miRNA;
Tax Domain:	Metazoa
Go:	0035195
So:	0001244
Entrezgene:	406904
Hgncid:	HGNC:31499
Omim:	609326
Chromosome:	20
Arm:	q
Band:	13.33

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.^[1] 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.

These micro RNAs have pivotal roles in development and physiology of muscle tissues including the heart.^{[2] [3]} MiR-1 is known to play an important role in heart diseases such as hypertrophy, myocardial infarction, and arrhythmias.^{[4] [5] [6]} Studies have shown that MiR-1 is an important regulator of heart adaption after ischemia or ischaemic stress and it is upregulated in the remote myocardium of patients with myocardial infarction.^[7] Also MiR-1 is downregulated in myocardial infarcted tissue compared to healthy heart tissue.^[8] Plasma levels of MiR-1 can be used as a sensitive biomarker for myocardial infarction.^[9]

Targets of miR-1

The heat shock protein, HSP60 is also known to be a target for post-transcriptional regulation by miR-1 and miR-206. HSP60 is a component of the defence mechanism against diabetic myocardial injury and its level is reduced in the diabetic myocardium. In both in vivo and in vitro experiments increased levels of glucose in myocardiomyctes led to significant upregulation of miR-1 and miR-206 with resulting modulation of HSP60 leading to accelerated glucose-mediated apoptosis in cardiomyocytes.^[10]

MiR-1 has key roles in the development and differentiation of smooth and skeletal muscles.^{[11] [12] [13]} For example, in the lineage-specific differentiation of smooth muscle cells from embryonic stem cell derived cultures, MiR-1 is required; as its loss of function resulted in a reduction in smooth muscle cell biomarkers and a reduction in the derived smooth muscle cell population. There is evidence that the control of smooth muscle cell differentiation by MiR-1 may be mediated by the down regulation of Kruppel-like factor 4 (KLF4), since a MiR-1 recognition site is predicted in the 3' UTR of KLF4 and inhibition of MiR-1 results in reversed down-regulation of KLF4 and an inhibition of smooth muscle cell differentiation.^[14] A mutation in the 3' UTR of the myostatin gene in Texel sheep creates a miR-1 and miR-206 target site. This is likely to cause the muscular phenotype of this breed of sheep.^[15]

Clinical relevance of miR-1

Mir-1 plays an important role in some cancers. Rhabdomyosarcoma is the most common soft tissue sarcoma in children. Since the tumor results from undifferentiated cells, agents that promote differentiation hold promise as possible therapies. A study showed that levels of mir-1 and mir-133a were drastically reduced in tumourous cell lines whilst their targets were up-regulated.^[16]

Introduction of miR-1 and miR-133a into an embryonal rhabdomyosarcoma-derived cell line is cytostatic, which suggested a strong tumour-suppressive role for these microRNAs. Expression of miR-1 but not miR-133a gave transcriptional profiles that were consistent with a strong promyogenic influence on the cells, again demonstrating the role of miR-1 in muscle differentiation from precursor stem cells. The authors propose that miR-1 and miR-133a act to repress isoforms of genes that are not normally expressed in muscle cells. All of these observations suggest that mis-regulation of miR-1 and miR-133a can result in tumorogenesis via abolition of the suppressive effect they have on certain gene targets and of the removal of the promotion of differentiation of the cells exerted my miR-1.^[16]

The involvement of miR-1 in cancer is not limited to cancers of muscle and muscle tissues. MiR-1 may have a tumour-suppressive effect in bladder cancer by regulation of LIM and SH3 protein 1 (LASP1).^[17]

There is evidence for the role of miR-1-2 as a modulator in acute myeloid leukemia via its transcription by the zinc-finger transcription factor, EVI1, ectopic virus expression site 1. ChIP assays have shown that EVI1 binds strongly to the promoters of miR-1-2 and miR-133-a-1, and expression of EVI1 is significantly correlated with the expression of miR-1-2 and miR-133-a-1 in established cell lines and in patient samples. However, only miR-1-2 was involved in abnormal proliferation in EVI1 expressing cell lines.^[18]

miR-1 and related microRNA miR-499 are proposed to be involved in the regulation of hepatocellular carcinoma (HCC) pathogenesis.^[19] These two microRNAs have been shown to downregulate the expression of the ets1 proto-oncogene in cell lines HepG2 by targeting the 3'UTR of ets1. ets1 is involved in extracellular matrix (ECM) degradation which is an important process required for tumor cell invasion and migration.

Further reading

• Xie C, Huang H, Sun X, Guo Y, Hamblin M, Ritchie RP, Garcia-Barrio MT, Zhang J, Chen YE . 6 . MicroRNA-1 regulates smooth muscle cell differentiation by repressing Kruppel-like factor 4 . Stem Cells and Development . 20 . 2 . 205–10 . February 2011 . 20799856 . 10.1089/scd.2010.0283 . 3128754 .
• Chen J, Yin H, Jiang Y, Radhakrishnan SK, Huang ZP, Li J, Shi Z, Kilsdonk EP, Gui Y, Wang DZ, Zheng XL . 6 . Induction of microRNA-1 by myocardin in smooth muscle cells inhibits cell proliferation . Arteriosclerosis, Thrombosis, and Vascular Biology . 31 . 2 . 368–75 . February 2011 . 21051663 . 10.1161/ATVBAHA.110.218149 . 3207238 .
• Sumiyoshi K, Kubota S, Ohgawara T, Kawata K, Nishida T, Shimo T, Yamashiro T, Takigawa M . 6 . Identification of miR-1 as a micro RNA that supports late-stage differentiation of growth cartilage cells . Biochemical and Biophysical Research Communications . 402 . 2 . 286–90 . November 2010 . 20937250 . 10.1016/j.bbrc.2010.10.016 .
• Li Q, Song XW, Zou J, Wang GK, Kremneva E, Li XQ, Zhu N, Sun T, Lappalainen P, Yuan WJ, Qin YW, Jing Q . 6 . Attenuation of microRNA-1 derepresses the cytoskeleton regulatory protein twinfilin-1 to provoke cardiac hypertrophy . Journal of Cell Science . 123 . Pt 14 . 2444–52 . July 2010 . 20571053 . 10.1242/jcs.067165 . 11750031 .
• Jiang Y, Yin H, Zheng XL . MicroRNA-1 inhibits myocardin-induced contractility of human vascular smooth muscle cells . Journal of Cellular Physiology . 225 . 2 . 506–11 . November 2010 . 20458751 . 10.1002/jcp.22230 . 45605427 .
• Cheng Y, Tan N, Yang J, Liu X, Cao X, He P, Dong X, Qin S, Zhang C . 6 . A translational study of circulating cell-free microRNA-1 in acute myocardial infarction . Clinical Science . 119 . 2 . 87–95 . April 2010 . 20218970 . 10.1042/CS20090645 . 3593815 .
• Sluijter JP, van Mil A, van Vliet P, Metz CH, Liu J, Doevendans PA, Goumans MJ . 6 . MicroRNA-1 and -499 regulate differentiation and proliferation in human-derived cardiomyocyte progenitor cells . Arteriosclerosis, Thrombosis, and Vascular Biology . 30 . 4 . 859–68 . April 2010 . 20081117 . 10.1161/ATVBAHA.109.197434 . free .
• Divakaran VG . MicroRNAs miR-1, -133 and -208: same faces, new roles . Cardiology . 115 . 3 . 172–3 . 2010 . 20068301 . 10.1159/000272540 . 45134661 .
• Girmatsion Z, Biliczki P, Bonauer A, Wimmer-Greinecker G, Scherer M, Moritz A, Bukowska A, Goette A, Nattel S, Hohnloser SH, Ehrlich JR . 6 . Changes in microRNA-1 expression and IK1 up-regulation in human atrial fibrillation . Heart Rhythm . 6 . 12 . 1802–9 . December 2009 . 19959133 . 10.1016/j.hrthm.2009.08.035 .
• Elia L, Contu R, Quintavalle M, Varrone F, Chimenti C, Russo MA, Cimino V, De Marinis L, Frustaci A, Catalucci D, Condorelli G . 6 . Reciprocal regulation of microRNA-1 and insulin-like growth factor-1 signal transduction cascade in cardiac and skeletal muscle in physiological and pathological conditions . Circulation . 120 . 23 . 2377–85 . December 2009 . 19933931 . 2825656 . 10.1161/CIRCULATIONAHA.109.879429 .
• Ai J, Zhang R, Li Y, Pu J, Lu Y, Jiao J, Li K, Yu B, Li Z, Wang R, Wang L, Li Q, Wang N, Shan H, Li Z, Yang B . 6 . Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction . Biochemical and Biophysical Research Communications . 391 . 1 . 73–7 . January 2010 . 19896465 . 10.1016/j.bbrc.2009.11.005 .
• Lin WC, Huang KY, Chen SC, Huang TY, Chen SJ, Huang PJ, Tang P . 6 . Malate dehydrogenase is negatively regulated by miR-1 in Trichomonas vaginalis . Parasitology Research . 105 . 6 . 1683–9 . November 2009 . 19777264 . 10.1007/s00436-009-1616-5 . 28947709 .
• Shan H, Li X, Pan Z, Zhang L, Cai B, Zhang Y, Xu C, Chu W, Qiao G, Li B, Lu Y, Yang B . 6 . Tanshinone IIA protects against sudden cardiac death induced by lethal arrhythmias via repression of microRNA-1 . British Journal of Pharmacology . 158 . 5 . 1227–35 . November 2009 . 19775284 . 2782332 . 10.1111/j.1476-5381.2009.00377.x .
• Yan D, Dong X, Chen X, Wang L, Lu C, Wang J, Qu J, Tu L . 6 . MicroRNA-1/206 targets c-Met and inhibits rhabdomyosarcoma development . The Journal of Biological Chemistry . 284 . 43 . 29596–604 . October 2009 . 19710019 . 2785592 . 10.1074/jbc.M109.020511 . free .
• Lu Y, Zhang Y, Shan H, Pan Z, Li X, Li B, Xu C, Zhang B, Zhang F, Dong D, Song W, Qiao G, Yang B . 6 . MicroRNA-1 downregulation by propranolol in a rat model of myocardial infarction: a new mechanism for ischaemic cardioprotection . Cardiovascular Research . 84 . 3 . 434–41 . December 2009 . 19581315 . 10.1093/cvr/cvp232 . free .
• Takaya T, Ono K, Kawamura T, Takanabe R, Kaichi S, Morimoto T, Wada H, Kita T, Shimatsu A, Hasegawa K . 6 . MicroRNA-1 and MicroRNA-133 in spontaneous myocardial differentiation of mouse embryonic stem cells . Circulation Journal . 73 . 8 . 1492–7 . August 2009 . 19521018 . 10.1253/circj.CJ-08-1032 . free .
• Tang Y, Zheng J, Sun Y, Wu Z, Liu Z, Huang G . MicroRNA-1 regulates cardiomyocyte apoptosis by targeting Bcl-2 . International Heart Journal . 50 . 3 . 377–87 . May 2009 . 19506341 . 10.1536/ihj.50.377 . free .
• Shan ZX, Lin QX, Fu YH, Deng CY, Zhou ZL, Zhu JN, Liu XY, Zhang YY, Li Y, Lin SG, Yu XY . 6 . Upregulated expression of miR-1/miR-206 in a rat model of myocardial infarction . Biochemical and Biophysical Research Communications . 381 . 4 . 597–601 . April 2009 . 19245789 . 10.1016/j.bbrc.2009.02.097 .
• Mishima Y, Abreu-Goodger C, Staton AA, Stahlhut C, Shou C, Cheng C, Gerstein M, Enright AJ, Giraldez AJ . 6 . Zebrafish miR-1 and miR-133 shape muscle gene expression and regulate sarcomeric actin organization . Genes & Development . 23 . 5 . 619–32 . March 2009 . 19240126 . 2658521 . 10.1101/gad.1760209 .
• Ikeda S, He A, Kong SW, Lu J, Bejar R, Bodyak N, Lee KH, Ma Q, Kang PM, Golub TR, Pu WT . 6 . MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes . Molecular and Cellular Biology . 29 . 8 . 2193–204 . April 2009 . 19188439 . 2663304 . 10.1128/MCB.01222-08 .
• Terentyev D, Belevych AE, Terentyeva R, Martin MM, Malana GE, Kuhn DE, Abdellatif M, Feldman DS, Elton TS, Györke S . 6 . miR-1 overexpression enhances Ca(2+) release and promotes cardiac arrhythmogenesis by targeting PP2A regulatory subunit B56alpha and causing CaMKII-dependent hyperphosphorylation of RyR2 . Circulation Research . 104 . 4 . 514–21 . February 2009 . 19131648 . 10.1161/CIRCRESAHA.108.181651 . 4394868 .
• Yu XY, Song YH, Geng YJ, Lin QX, Shan ZX, Lin SG, Li Y . 6 . Glucose induces apoptosis of cardiomyocytes via microRNA-1 and IGF-1 . Biochemical and Biophysical Research Communications . 376 . 3 . 548–52 . November 2008 . 18801338 . 10.1016/j.bbrc.2008.09.025 .
• Sweetman D, Goljanek K, Rathjen T, Oustanina S, Braun T, Dalmay T, Münsterberg A . 6 . Specific requirements of MRFs for the expression of muscle specific microRNAs, miR-1, miR-206 and miR-133 . Developmental Biology . 321 . 2 . 491–9 . September 2008 . 18619954 . 10.1016/j.ydbio.2008.06.019 .
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• Yang B, Lin H, Xiao J, Lu Y, Luo X, Li B, Zhang Y, Xu C, Bai Y, Wang H, Chen G, Wang Z . 6 . The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2 . Nature Medicine . 13 . 4 . 486–91 . April 2007 . 17401374 . 10.1038/nm1569 . 1935811 .
• Mishima T, Mizuguchi Y, Kawahigashi Y, Takizawa T, Takizawa T . RT-PCR-based analysis of microRNA (miR-1 and -124) expression in mouse CNS . Brain Research . 1131 . 1 . 37–43 . February 2007 . 17182009 . 10.1016/j.brainres.2006.11.035 . 23792536 .
• Nakajima N, Takahashi T, Kitamura R, Isodono K, Asada S, Ueyama T, Matsubara H, Oh H . MicroRNA-1 facilitates skeletal myogenic differentiation without affecting osteoblastic and adipogenic differentiation . Biochemical and Biophysical Research Communications . 350 . 4 . 1006–12 . December 2006 . 17045567 . 10.1016/j.bbrc.2006.09.153 .
• McCarthy JJ, Esser KA . MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy . Journal of Applied Physiology . 102 . 1 . 306–13 . January 2007 . 17008435 . 10.1152/japplphysiol.00932.2006 .
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External links

• • miRBase Entry for human mir-1-1
• Ensembl gene page for human mir-1-1
• NCBI Entrez gene page for human mir-1-1

Notes and References

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3. Zhao Y, Ransom JF, Li A, Vedantham V, von Drehle M, Muth AN, Tsuchihashi T, McManus MT, Schwartz RJ, Srivastava D . 6 . Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2 . Cell . 129 . 2 . 303–17 . April 2007 . 17397913 . 10.1016/j.cell.2007.03.030 . 10796290 . free .
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5. Silvestri P, Di Russo C, Rigattieri S, Fedele S, Todaro D, Ferraiuolo G, Altamura G, Loschiavo P . 6 . MicroRNAs and ischemic heart disease: towards a better comprehension of pathogenesis, new diagnostic tools and new therapeutic targets . Recent Patents on Cardiovascular Drug Discovery . 4 . 2 . 109–18 . June 2009 . 19519553 . 10.2174/157489009788452977 .
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10. Shan ZX, Lin QX, Deng CY, Zhu JN, Mai LP, Liu JL, Fu YH, Liu XY, Li YX, Zhang YY, Lin SG, Yu XY . 6 . miR-1/miR-206 regulate Hsp60 expression contributing to glucose-mediated apoptosis in cardiomyocytes . FEBS Letters . 584 . 16 . 3592–600 . August 2010 . 20655308 . 10.1016/j.febslet.2010.07.027 . 38053878 .
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14. Xie C, Huang H, Sun X, Guo Y, Hamblin M, Ritchie RP, Garcia-Barrio MT, Zhang J, Chen YE . 6 . MicroRNA-1 regulates smooth muscle cell differentiation by repressing Kruppel-like factor 4 . Stem Cells and Development . 20 . 2 . 205–10 . February 2011 . 20799856 . 3128754 . 10.1089/scd.2010.0283 .
15. Clop A, Marcq F, Takeda H, Pirottin D, Tordoir X, Bibé B, Bouix J, Caiment F, Elsen JM, Eychenne F, Larzul C, Laville E, Meish F, Milenkovic D, Tobin J, Charlier C, Georges M . 6 . A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep . Nature Genetics . 38 . 7 . 813–8 . July 2006 . 16751773 . 10.1038/ng1810 . 39767621 .
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17. Chiyomaru T, Enokida H, Kawakami K, Tatarano S, Uchida Y, Kawahara K, Nishiyama K, Seki N, Nakagawa M . 6 . Functional role of LASP1 in cell viability and its regulation by microRNAs in bladder cancer . Urologic Oncology . 30 . 4 . 434–43 . 2010 . 20843712 . 10.1016/j.urolonc.2010.05.008 .
18. Gómez-Benito M, Conchillo A, García MA, Vázquez I, Maicas M, Vicente C, Cristobal I, Marcotegui N, García-Ortí L, Bandrés E, Calasanz MJ, Alonso MM, Odero MD . 6 . EVI1 controls proliferation in acute myeloid leukaemia through modulation of miR-1-2 . British Journal of Cancer . 103 . 8 . 1292–6 . October 2010 . 20842122 . 2967053 . 10.1038/sj.bjc.6605874 .
19. Wei W, Hu Z, Fu H, Tie Y, Zhang H, Wu Y, Zheng X . 6 . MicroRNA-1 and microRNA-499 downregulate the expression of the proto-oncogene in HepG2 cells . Oncology Reports . 28 . 2 . 701–6 . August 2012 . 22664953 . 10.3892/or.2012.1850 . free .