Mir-221 microRNA explained

mir-221
Symbol:	mir-221
Rfam:	RF00651
Mirbase Family:	MIPF0000051
Rna Type:	microRNA
Tax Domain:	Eukaryota Vertebrata;
Hgncid:	31601
Omim:	300568

In molecular biology, mir-221 microRNA (and its paralogue, mir-222) is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

mir-221 is an oncogenic microRNA.^[1] It targets CD117, which then prevents cell migration and proliferation in endothelial cells.^{[2] [3]} miR-221 is known as an anti angiogenic miRNA.^{[4] [2]} Recent important studies have reported that miR-221 is also involved in induction of angiogenesis.^{[5] [6] [7]} RNA induced Silencing Complex (RISC) proteins SND1 and AEG-1 induces miR-221 expression in Liver cancer.^[8] In liver cancer miR-221 induces the tumor angiogenesis.^[5] miR-221 detection in human faeces can be a non-invasive screening marker for colorectal cancer.^[9]

miR-221 has been identified as playing a role in androgenetic alopecia.^[10]

See also

• MicroRNA

Further reading

• Zhang C, Zhang J, Zhang A, Wang Y, Han L, You Y, Pu P, Kang C . PUMA is a novel target of miR-221/222 in human epithelial cancers . Int J Oncol . 37 . 6 . 1621–6 . 2010 . 21042732 . 10.3892/ijo_00000816. free .
• Pu XX, Huang GL, Guo HQ, Guo CC, Li H, Ye S, Ling S, Jiang L, Tian Y, Lin TY . Circulating miR-221 directly amplified from plasma is a potential diagnostic and prognostic marker of colorectal cancer and is correlated with p53 expression . J Gastroenterol Hepatol . 25 . 10 . 1674–80 . 2010 . 20880178 . 10.1111/j.1440-1746.2010.06417.x. 34881675 .
• Kedde M, van Kouwenhove M, Zwart W, Oude Vrielink JA, Elkon R, Agami R . A Pumilio-induced RNA structure switch in p27–3' UTR controls miR-221 and miR-222 accessibility . Nat Cell Biol . 12 . 10 . 1014–20 . 2010 . 20818387 . 10.1038/ncb2105. 205286991 .
• Zhang CZ, Zhang JX, Zhang AL, Shi ZD, Han L, Jia ZF, Yang WD, Wang GX, Jiang T, You YP, Pu PY, Cheng JQ, Kang CS . MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma . Mol Cancer . 9 . 229 . 2010 . 20813046 . 10.1186/1476-4598-9-229 . 2939570 . free .
• Dai R, Li J, Liu Y, Yan D, Chen S, Duan C, Liu X, He T, Li H . miR-221/222 suppression protects against endoplasmic reticulum stress-induced apoptosis via p27(Kip1)- and MEK/ERK-mediated cell cycle regulation . Biol Chem . 391 . 7 . 791–801 . 2010 . 20624000 . 10.1515/BC.2010.072. 23085890 .
• Chun-Zhi Z, Lei H, An-Ling Z, Yan-Chao F, Xiao Y, Guang-Xiu W, Zhi-Fan J, Pei-Yu P, Qing-Yu Z, Chun-Sheng K . MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN . BMC Cancer . 10. 367 . 2010 . 20618998 . 10.1186/1471-2407-10-367 . 2914702 . free .
• Das SK, Sokhi UK, Bhutia SK, Azab B, Su ZZ, Sarkar D, Fisher PB . Human polynucleotide phosphorylase selectively and preferentially degrades microRNA-221 in human melanoma cells . Proc Natl Acad Sci U S A . 107 . 26 . 11948–53 . 2010 . 20547861 . 10.1073/pnas.0914143107 . 2900648. free . 2010PNAS..10711948D .
• Chen Y, Banda M, Speyer CL, Smith JS, Rabson AB, Gorski DH . Regulation of the expression and activity of the antiangiogenic homeobox gene GAX/MEOX2 by ZEB2 and microRNA-221 . Mol Cell Biol . 30 . 15 . 3902–13 . 2010 . 20516212 . 10.1128/MCB.01237-09 . 2916411.
• Wurz K, Garcia RL, Goff BA, Mitchell PS, Lee JH, Tewari M, Swisher EM . MiR-221 and MiR-222 alterations in sporadic ovarian carcinoma: Relationship to CDKN1B, CDKNIC and overall survival . Genes Chromosomes Cancer . 49 . 7 . 577–584 . 2010 . 20461750 . 10.1002/gcc.20768 . 2869465.
• Zhang C, Han L, Zhang A, Yang W, Zhou X, Pu P, Du Y, Zeng H, Kang C . Global changes of mRNA expression reveals an increased activity of the interferon-induced signal transducer and activator of transcription (STAT) pathway by repression of miR-221/222 in glioblastoma U251 cells . Int J Oncol . 36 . 6 . 1503–12 . 2010 . 20428775 . 10.3892/ijo_00000637. free .
• Gabbianelli M, Testa U, Morsilli O, Pelosi E, Saulle E, Petrucci E, Castelli G, Giovinazzi S, Mariani G, Fiori ME, Bonanno G, Massa A, Croce CM, Fontana L, Peschle C . Mechanism of human Hb switching: a possible role of the kit receptor/miR 221–222 complex . Haematologica . 95 . 8 . 1253–60 . 2010 . 20305142 . 10.3324/haematol.2009.018259 . 2913072.
• Frenquelli M, Muzio M, Scielzo C, Fazi C, Scarfò L, Rossi C, Ferrari G, Ghia P, Caligaris-Cappio F . MicroRNA and proliferation control in chronic lymphocytic leukemia: functional relationship between miR-221/222 cluster and p27 . Blood . 115 . 19 . 3949–59 . 2010 . 20203269 . 10.1182/blood-2009-11-254656. free .
• Zhang J, Han L, Ge Y, Zhou X, Zhang A, Zhang C, Zhong Y, You Y, Pu P, Kang C . miR-221/222 promote malignant progression of glioma through activation of the Akt pathway . Int J Oncol . 36 . 4 . 913–920 . 2010 . 20198336 . 10.3892/ijo_00000570. free .
• Fu X, Wang Q, Chen J, Huang X, Chen X, Cao L, Tan H, Li W, Zhang L, Bi J, Su Q, Chen L . Clinical significance of miR-221 and its inverse correlation with p27(Kip1) in hepatocellular carcinoma . Mol Biol Rep . 38. 5. 3029–35. 2010 . 20146005 . 10.1007/s11033-010-9969-5. 24880277 .
• Hu G, Gong AY, Liu J, Zhou R, Deng C, Chen XM . miR-221 suppresses ICAM-1 translation and regulates interferon-gamma-induced ICAM-1 expression in human cholangiocytes . Am J Physiol Gastrointest Liver Physiol . 298 . 4 . G542–50 . 2010 . 20110463 . 10.1152/ajpgi.00490.2009 . 2853302.
• Zhao P, Fu Z, You YP, Lu XM, Lu AL, Liu N . [Construction and screening an effective anti-miR-221 RNAi vector in vitro] . Sichuan da Xue Xue Bao Yi Xue Ban . 40 . 6 . 973–7 . 2009 . 20067101.
• Zhang CZ, Kang CS, Pu PY, Wang GX, Jia ZF, Zhang AL, Han L, Xu P . [Inhibitory effect of knocking down microRNA-221 and microRNA-222 on glioma cell growth in vitro and in vivo] . Zhonghua Zhong Liu Za Zhi . 31 . 10 . 721–6 . 2009 . 20021821.
• Pineau P, Volinia S, McJunkin K, Marchio A, Battiston C, Terris B, Mazzaferro V, Lowe SW, Croce CM, Dejean A . miR-221 overexpression contributes to liver tumorigenesis . Proc Natl Acad Sci U S A . 107 . 1 . 264–9 . 2010 . 20018759 . 10.1073/pnas.0907904107 . 2806773. free . 2010PNAS..107..264P .
• Sredni ST, Bonaldo Mde F, Costa FF, Huang CC, Hamm CA, Rajaram V, Tomita T, Goldman S, Bischof JM, Soares MB . Upregulation of mir-221 and mir-222 in atypical teratoid/rhabdoid tumors: potential therapeutic targets . Childs Nerv Syst . 26 . 3 . 279–283 . 2010 . 20012062 . 10.1007/s00381-009-1028-y. 25199512 .
• Zhang C, Wang G, Kang C, Du Y, Pu P . [Up-regulation of p27(kip1) by miR-221/222 antisense oligonucleotides enhances the radiosensitivity of U251 glioblastoma] . Zhonghua Yi Xue Yi Chuan Xue Za Zhi . 26 . 6 . 634–8 . 2009 . 19953484 . 10.3760/cma.j.issn.1003-9406.2009.06.006.
• Cardinali B, Castellani L, Fasanaro P, Basso A, Alemà S, Martelli F, Falcone G . Microrna-221 and microrna-222 modulate differentiation and maturation of skeletal muscle cells . PLOS ONE. 4 . 10 . e7607 . 2009 . 19859555 . 10.1371/journal.pone.0007607 . Ng . Irene Oi-Lin . 2762614. free . 2009PLoSO...4.7607C .
• Lu Q, Lu C, Zhou GP, Zhang W, Xiao H, Wang XR . MicroRNA-221 silencing predisposed human bladder cancer cells to undergo apoptosis induced by TRAIL . Urol Oncol . 28. 6. 635–641. 2009 . 19767219 . 10.1016/j.urolonc.2009.06.005.
• Kotani A, Ha D, Hsieh J, Rao PK, Schotte D, den Boer ML, Armstrong SA, Lodish HF . miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221 . Blood . 114 . 19 . 4169–78 . 2009 . 19749093 . 10.1182/blood-2008-12-191619 . 2774553.
• Gramantieri L, Fornari F, Ferracin M, Veronese A, Sabbioni S, Calin GA, Grazi GL, Croce CM, Bolondi L, Negrini M . MicroRNA-221 targets Bmf in hepatocellular carcinoma and correlates with tumor multifocality . Clin Cancer Res . 15 . 16 . 5073–81 . 2009 . 19671867 . 10.1158/1078-0432.CCR-09-0092. 3900721 .
• Sun T, Yang M, Kantoff P, Lee GS . Role of microRNA-221/-222 in cancer development and progression . Cell Cycle . 8 . 15 . 2315–6 . 2009 . 19625765 . 10.4161/cc.8.15.9221. 2636213 . free .
• Spahn M, Kneitz S, Scholz CJ, Stenger N, Rüdiger T, Ströbel P, Riedmiller H, Kneitz B . Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrence . Int J Cancer . 127 . 2 . 394–403 . 2010 . 19585579 . 10.1002/ijc.24715. 23769033 . free .
• Terasawa K, Ichimura A, Sato F, Shimizu K, Tsujimoto G . Sustained activation of ERK1/2 by NGF induces microRNA-221 and 222 in PC12 cells . FEBS J . 276 . 12 . 3269–76 . 2009 . 19438724 . 10.1111/j.1742-4658.2009.07041.x. 36686669 .
• Zhang C, Kang C, You Y, Pu P, Yang W, Zhao P, Wang G, Zhang A, Jia Z, Han L, Jiang H . Co-suppression of miR-221/222 cluster suppresses human glioma cell growth by targeting p27kip1 in vitro and in vivo . Int J Oncol . 34 . 6 . 1653–60 . 2009 . 19424584 . 10.3892/ijo_00000296. free .
• Minami Y, Satoh M, Maesawa C, Takahashi Y, Tabuchi T, Itoh T, Nakamura M . Effect of atorvastatin on microRNA 221 / 222 expression in endothelial progenitor cells obtained from patients with coronary artery disease . Eur J Clin Invest . 39 . 5 . 359–367 . 2009 . 19371267 . 10.1111/j.1365-2362.2009.02110.x. 205291066 . free .
• Sun T, Wang Q, Balk S, Brown M, Lee GS, Kantoff P . The role of microRNA-221 and microRNA-222 in androgen-independent prostate cancer cell lines . Cancer Res . 69 . 8 . 3356–63 . 2009 . 19351832 . 10.1158/0008-5472.CAN-08-4112 . 2703812.
• Li Y, Song YH, Li F, Yang T, Lu YW, Geng YJ . MicroRNA-221 regulates high glucose-induced endothelial dysfunction . Biochem Biophys Res Commun . 381 . 1 . 81–83 . 2009 . 19351599 . 10.1016/j.bbrc.2009.02.013 . 2670889.
• Liu X, Cheng Y, Zhang S, Lin Y, Yang J, Zhang C . A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia . Circ Res . 104 . 4 . 476–487 . 2009 . 19150885 . 10.1161/CIRCRESAHA.108.185363 . 2728290.
• Mayoral RJ, Pipkin ME, Pachkov M, van Nimwegen E, Rao A, Monticelli S . MicroRNA-221-222 regulate the cell cycle in mast cells . Journal of Immunology . 182 . 1 . 433–445 . 2009 . 19109175 . 2610349 . 10.4049/jimmunol.182.1.433.
• Mercatelli N, Coppola V, Bonci D, Miele F, Costantini A, Guadagnoli M, Bonanno E, Muto G, Frajese GV, De Maria R, Spagnoli LG, Farace MG, Ciafrè SA . The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice . PLOS ONE. 3 . 12 . e4029 . 2008 . 19107213 . 10.1371/journal.pone.0004029 . Blagosklonny . Mikhail V. . 2603596. free . 2008PLoSO...3.4029M .
• Davis BN, Hilyard AC, Nguyen PH, Lagna G, Hata A . Induction of microRNA-221 by platelet-derived growth factor signaling is critical for modulation of vascular smooth muscle phenotype . J Biol Chem . 284 . 6 . 3728–38 . 2009 . 19088079 . 10.1074/jbc.M808788200 . 2635044. free .
• Kim HJ, Chung JK, Hwang do W, Lee DS, Kim S . In vivo imaging of miR-221 biogenesis in papillary thyroid carcinoma . Mol Imaging Biol . 11 . 2 . 71–78 . 2008. 19030936 . 10.1007/s11307-008-0188-6. 10368716 .
• Felicetti F, Errico MC, Segnalini P, Mattia G, Carè A . MicroRNA-221 and -222 pathway controls melanoma progression . Expert Rev Anticancer Ther . 8 . 11 . 1759–65 . 2008 . 18983236 . 10.1586/14737140.8.11.1759. 2438171 .
• Kim HJ, Kim YH, Lee DS, Chung JK, Kim S . In vivo imaging of functional targeting of miR-221 in papillary thyroid carcinoma . J Nucl Med . 49 . 10 . 1686–93 . 2008 . 18794255 . 10.2967/jnumed.108.052894. 16600024 . free . 10371/67771 . free .
• Miller TE, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro CL, Jacob S, Majumder S . MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1 . J Biol Chem . 283 . 44 . 29897–903 . 2008 . 18708351 . 10.1074/jbc.M804612200 . 2573063. free .
• Fornari F, Gramantieri L, Ferracin M, Veronese A, Sabbioni S, Calin GA, Grazi GL, Giovannini C, Croce CM, Bolondi L, Negrini M . MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma . Oncogene . 27 . 43 . 5651–61 . 2008 . 18521080 . 10.1038/onc.2008.178. 19800498 .
• Felicetti F, Errico MC, Bottero L, Segnalini P, Stoppacciaro A, Biffoni M, Felli N, Mattia G, Petrini M, Colombo MP, Peschle C, Carè A . The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms . Cancer Res . 68 . 8 . 2745–54 . 2008 . 18417445 . 10.1158/0008-5472.CAN-07-2538. free .
• Visone R, Russo L, Pallante P, De Martino I, Ferraro A, Leone V, Borbone E, Petrocca F, Alder H, Croce CM, Fusco A . MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle . Endocr Relat Cancer . 14 . 3 . 791–8 . 2007 . 17914108 . 10.1677/ERC-07-0129. free .
• le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, Mangiola A, Anile C, Maira G, Mercatelli N, Ciafrè SA, Farace MG, Agami R . Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation . The EMBO Journal. 26 . 15 . 3699–3708 . 2007 . 17627278 . 10.1038/sj.emboj.7601790 . 1949005.
• Galardi S, Mercatelli N, Giorda E, Massalini S, Frajese GV, Ciafrè SA, Farace MG . miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1 . J Biol Chem . 282 . 32 . 23716–24 . 2007 . 17569667 . 10.1074/jbc.M701805200. free .

Notes and References

1. Pang. Y . Young, CY . Yuan, H. MicroRNAs and prostate cancer.. Acta Biochimica et Biophysica Sinica. 15 June 2010. 42. 6. 363–9. 20539944. 10.1093/abbs/gmq038.
2. Urbich. C. Kuehbacher, A . Dimmeler, S . Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovascular Research. 1 September 2008. 79. 4. 581–8. 18550634. 10.1093/cvr/cvn156.
3. Vasilatou. D. Papageorgiou, S . Pappa, V . Papageorgiou, E . Dervenoulas, J . The role of microRNAs in normal and malignant hematopoiesis. European Journal of Haematology. 1 January 2010. 84. 1. 1–16. 19744129. 10.1111/j.1600-0609.2009.01348.x. 46395419. free.
4. Kuehbacher A, Urbich C, Dimmeler S . Targeting microRNA expression to regulate angiogenesis . Trends Pharmacol Sci . 29 . 1 . 12–15 . 2008 . 18068232 . 10.1016/j.tips.2007.10.014.
5. Santhekadur PK, Das SK, Gredler R, Chen D, Srivastava J, Robertson C, Baldwin AS, Fisher PB, Sarkar D . Multifunction protein staphylococcal nuclease domain containing 1 (SND1) promotes tumor angiogenesis in human hepatocellular carcinoma through novel pathway that involves nuclear factor κB and miR-221 . J Biol Chem . 287 . 17 . 13952–8 . 2012 . 22396537 . 10.1074/jbc.M111.321646 . 3340184. free .
6. Nicoli S, Knyphausen CP, Zhu LJ, Lakshmanan A, Lawson ND . miR-221 is required for endothelial tip cell behaviors during vascular development . Dev Cell . 22 . 2 . 418–429 . 2012 . 22340502 . 10.1016/j.devcel.2012.01.008 . 3285411.
7. Le Bot. Nathalie. MicroRNAs in angiogenesis. Nat. Cell Biol.. 2 April 2012. 14. 4. 342. 10.1038/ncb2484. 45572115. free.
8. Yoo BK, Santhekadur PK, Gredler R, Chen D, Emdad L, Bhutia S, Pannell L, Fisher PB, Sarkar D . Increased RNA-induced silencing complex (RISC) activity contributes to hepatocellular carcinoma . Hepatology . 53 . 5 . 1538–48 . 2011 . 21520169 . 10.1002/hep.24216 . 3081619.
9. microRNA-221 and microRNA-18a identification in stool as potential biomarkers for the non-invasive diagnosis of colorectal carcinoma. British Journal of Cancer. 2014-10-28. 0007-0920. 4453736. 25233396. 1765–71. 111. 9. 10.1038/bjc.2014.484. T. O.. Yau. C. W.. Wu. Y.. Dong. C.-M.. Tang. S. S. M.. Ng. F. K. L.. Chan. J. J. Y.. Sung. J.. Yu.
10. Li K, Sun Y, Liu S, Zhou Y, Qu Q, Wang G, Wang J, Chen R, Fan Z, Liu B, Li Y, Mao X, Hu Z, Miao Y . The AR/miR-221/IGF-1 pathway mediates the pathogenesis of androgenetic alopecia . Int J Biol Sci . 19 . 11 . 3307–23 . 2023 . 37496996 . 10367565 . 10.7150/ijbs.80481 .