Genomes and Genes
Gene Symbol: MIR221
Description: microRNA 221
Alias: MIRN221, miRNA221, mir-221
- Garofalo M, Di Leva G, Romano G, Nuovo G, Suh S, Ngankeu A, et al. miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell. 2009;16:498-509 pubmed publisher..Finally, we demonstrate that the MET oncogene is involved in miR-221&222 activation through the c-Jun transcription factor. ..
- Dai R, Li J, Liu Y, Yan D, Chen S, Duan C, et al. miR-221/222 suppression protects against endoplasmic reticulum stress-induced apoptosis via p27(Kip1)- and MEK/ERK-mediated cell cycle regulation. Biol Chem. 2010;391:791-801 pubmed publisher..Our results suggest that suppression of miR-221/222 plays a crucial role in the protection against apoptosis induced by ER stress in HCC cells. ..
- Pu X, Huang G, Guo H, Guo C, Li H, Ye S, et al. 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. 2010;25:1674-80 pubmed publisher..The direct amplification of plasma miR-221 can be used as a potential noninvasive molecular marker for diagnosis and prognosis of CRC and is correlated with p53 expression. ..
- Duncavage E, Goodgame B, Sezhiyan A, Govindan R, Pfeifer J. Use of microRNA expression levels to predict outcomes in resected stage I non-small cell lung cancer. J Thorac Oncol. 2010;5:1755-63 pubmed publisher..If confirmed in prospective studies, miRNA expression in resected NSCLC could potentially identify those at high risk of relapse after surgery. ..
- Igoucheva O, Alexeev V. MicroRNA-dependent regulation of cKit in cutaneous melanoma. Biochem Biophys Res Commun. 2009;379:790-4 pubmed publisher..They also suggest that regulation of expression and functional activity of identified up-regulated miRNAs should be further studied in the context of malignant melanoma. ..
- Quintavalle C, Garofalo M, Zanca C, Romano G, Iaboni M, Del Basso De Caro M, et al. miR-221/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTP?. Oncogene. 2012;31:858-68 pubmed publisher..In conclusion, our results suggest that miR-221 and -222 regulate glioma tumorigenesis at least in part through the control of PTP? protein expression. ..
- Amankwah E, Anegbe E, Park H, Pow Sang J, Hakam A, Park J. miR-21, miR-221 and miR-222 expression and prostate cancer recurrence among obese and non-obese cases. Asian J Androl. 2013;15:226-30 pubmed publisher..Future larger studies are warranted to confirm these initial findings and to elucidate the mechanisms involved. ..
- Zhang C, Zhang J, Hao J, Shi Z, Wang Y, Han L, et al. High level of miR-221/222 confers increased cell invasion and poor prognosis in glioma. J Transl Med. 2012;10:119 pubmed publisher..The present data indicate that miR-221 and miR-222 directly regulate cell invasion by targeting TIMP3 and act as prognostic factors for glioma patients. ..
- Frenquelli M, Muzio M, Scielzo C, Fazi C, Scarfo L, Rossi C, et al. MicroRNA and proliferation control in chronic lymphocytic leukemia: functional relationship between miR-221/222 cluster and p27. Blood. 2010;115:3949-59 pubmed publisher..These data indicate that the miR-221/222 cluster modulates the expression of p27 protein in CLL cells and lead to suggest that miR-221/222 and p27 may represent a regulatory loop that helps maintaining CLL cells in a resting condition. ..
- Lambertini E, Lolli A, Vezzali F, Penolazzi L, Gambari R, Piva R. Correlation between Slug transcription factor and miR-221 in MDA-MB-231 breast cancer cells. BMC Cancer. 2012;12:445 pubmed publisher..These studies suggest that miR-221 expression is, in part, dependent on Slug in breast cancer cells, and that Slug plays a more important role than miR-221 in cell migration and invasion. ..
- Visone R, Russo L, Pallante P, De Martino I, Ferraro A, Leone V, et al. MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle. Endocr Relat Cancer. 2007;14:791-8 pubmed..Therefore, the data reported here demonstrate that miR-221 and miR-222 are endogenous regulators of p27(Kip1) protein expression, and thereby, the cell cycle. ..
- Stinson S, Lackner M, Adai A, Yu N, Kim H, O Brien C, et al. miR-221/222 targeting of trichorhinophalangeal 1 (TRPS1) promotes epithelial-to-mesenchymal transition in breast cancer. Sci Signal. 2011;4:pt5 pubmed publisher..TRPS1 inhibited EMT by directly repressing expression of ZEB2 (Zinc finger E-box-binding homeobox 2). Therefore, miR-221/222 may contribute to the aggressive clinical behavior of basal-like breast cancers. ..
- Zhao R, Wu J, Jia W, Gong C, Yu F, Ren Z, et al. Plasma miR-221 as a predictive biomarker for chemoresistance in breast cancer patients who previously received neoadjuvant chemotherapy. Onkologie. 2011;34:675-80 pubmed publisher..044) but not in the pathologic complete response rate (p = 0.477). Our results indicate that plasma miR-221 may be a predictive biomarker for sensitivity to NAC in breast cancer patients. ..
- Liu K, Li G, Fan C, Diao Y, Wu B, Li J. Increased Expression of MicroRNA-221 in gastric cancer and its clinical significance. J Int Med Res. 2012;40:467-74 pubmed..These findings suggest that miR-221 is a novel prognostic indicator in gastric cancer and may be a potential target for diagnosis and gene therapy. ..
- He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, et al. The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci U S A. 2005;102:19075-80 pubmed..We conclude that up-regulation of several miRs and regulation of KIT are involved in PTC pathogenesis, and that sequence changes in genes targeted by miRNAs can contribute to their regulation. ..
- Lupini L, Bassi C, Ferracin M, Bartonicek N, D Abundo L, Zagatti B, et al. miR-221 affects multiple cancer pathways by modulating the level of hundreds messenger RNAs. Front Genet. 2013;4:64 pubmed publisher..The modulation of mRNA level of 602 genes confirms the ability of miR-221 to promote cancer by affecting multiple oncogenic pathways. ..
- Fu X, Wang Q, Chen J, Huang X, Chen X, Cao L, et al. Clinical significance of miR-221 and its inverse correlation with p27Kip¹ in hepatocellular carcinoma. Mol Biol Rep. 2011;38:3029-35 pubmed publisher..In conclusion, miR-221 is important in tumorigenesis of HCC, possibly by specifically down-regulating p27(Kip1), a cell-cycle inhibitor. These results indicate miR-221 as a new therapeutic target in HCC. ..
- Park J, Lee E, Esau C, Schmittgen T. Antisense inhibition of microRNA-21 or -221 arrests cell cycle, induces apoptosis, and sensitizes the effects of gemcitabine in pancreatic adenocarcinoma. Pancreas. 2009;38:e190-9 pubmed publisher..We demonstrate that antisense to miR-21 and miR-221 results in significant cell killing under various conditions and that antisense oligonucleotides targeted to miRNA represents a potential new therapy for pancreatic cancer. ..
- Li Y, Song Y, Li F, Yang T, Lu Y, Geng Y. MicroRNA-221 regulates high glucose-induced endothelial dysfunction. Biochem Biophys Res Commun. 2009;381:81-3 pubmed publisher..These findings suggest that manipulation of the miR-221-c-kit pathway may offer a novel strategy for treatment of vascular dysfunction in diabetic patients. ..
- Davis B, Hilyard A, Nguyen P, 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. 2009;284:3728-38 pubmed publisher..Our study demonstrates that PDGF signaling, by modulating the expression of miR-221, regulates two critical determinants of the vSMC phenotype; they are SMC gene expression and cell proliferation. ..
- Panarelli N, Chen Y, Zhou X, Kitabayashi N, Yantiss R. MicroRNA expression aids the preoperative diagnosis of pancreatic ductal adenocarcinoma. Pancreas. 2012;41:685-90 pubmed publisher..001, respectively). Pancreatic ductal adenocarcinomas show differential expression of miRNAs compared to benign pancreatic lesions. A select panel of miRNAs aids the distinction between pancreatic lesions in cytology specimens. ..
- Galardi S, Mercatelli N, Giorda E, Massalini S, Frajese G, Ciafrè S, et al. miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1. J Biol Chem. 2007;282:23716-24 pubmed
- Miller T, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro C, et al. MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem. 2008;283:29897-903 pubmed publisher..This finding also provides the rationale for the application of altered expression of specific miRNAs as a predictive tamoxifen-resistant breast cancer marker. ..
- Zhang X, Mao H, Chen J, Wen S, Li D, Ye M, et al. Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway. Biochem Biophys Res Commun. 2013;431:404-8 pubmed publisher..Overall, these findings demonstrate that miR-221 affects the MEK/ERK pathway by targeting PAK1 to inhibit the proliferation of EPCs. ..
- Ogawa T, Enomoto M, Fujii H, Sekiya Y, Yoshizato K, Ikeda K, et al. MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis. Gut. 2012;61:1600-9 pubmed..miR-221/222 may be new markers for stellate cell activation and liver fibrosis progression. ..
- Sun T, Wang X, He H, Sweeney C, Liu S, Brown M, et al. MiR-221 promotes the development of androgen independence in prostate cancer cells via downregulation of HECTD2 and RAB1A. Oncogene. 2014;33:2790-800 pubmed publisher..We hypothesize that a major biological consequence of upregulation of miR-221 is reprogramming of AR signaling, which in turn may mediate the transition to the CRPC phenotype. ..
- Zhang J, Han L, Ge Y, Zhou X, Zhang A, Zhang C, et al. miR-221/222 promote malignant progression of glioma through activation of the Akt pathway. Int J Oncol. 2010;36:913-20 pubmed..Our results suggest that miR-221/222 co-enhance the glioma malignant phenotype via activation of the Akt pathway mediated by regulation of common gene expression. ..
- Lu Q, Lu C, Zhou G, Zhang W, Xiao H, Wang X. MicroRNA-221 silencing predisposed human bladder cancer cells to undergo apoptosis induced by TRAIL. Urol Oncol. 2010;28:635-41 pubmed publisher..MiRNA-221 silencing rendered human bladder cancer T24 cells to undergo apoptosis induced by TRAIL. Our findings suggest a potential role of suppressing miRNA-221 in human bladder cancer therapy. ..
- Park J, Kogure T, Nuovo G, Jiang J, He L, Kim J, et al. miR-221 silencing blocks hepatocellular carcinoma and promotes survival. Cancer Res. 2011;71:7608-16 pubmed publisher..Taken together, our findings offer a preclinical proof of efficacy for chol-anti-miR-221 in a valid orthotopic mouse model of HCC, suggesting that this targeted agent could benefit treatment for patients with advanced HCC. ..
- Hwang M, Yu N, Stinson S, Yue P, Newman R, Allan B, et al. miR-221/222 targets adiponectin receptor 1 to promote the epithelial-to-mesenchymal transition in breast cancer. PLoS ONE. 2013;8:e66502 pubmed publisher..These results suggest that ADIPOR1 may play an important role in breast cancer progression and metastasis, and could potentially offer an alternative therapeutic strategy for basal-like breast cancer patients. ..
- Fornari F, Gramantieri L, Ferracin M, Veronese A, Sabbioni S, Calin G, et al. MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene. 2008;27:5651-61 pubmed publisher..These findings establish a basis toward the development of therapeutic strategies aimed at blocking miR-221 in HCC. ..
- Garofalo M, Quintavalle C, Di Leva G, Zanca C, Romano G, Taccioli C, et al. MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer. Oncogene. 2008;27:3845-55 pubmed publisher..In conclusion, we show that high expression levels of miR-221 and -222 are needed to maintain the TRAIL-resistant phenotype, thus making these miRs as promising therapeutic targets or diagnostic tool for TRAIL resistance in NSCLC. ..
- Mercatelli N, Coppola V, Bonci D, Miele F, Costantini A, Guadagnoli M, et al. The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice. PLoS ONE. 2008;3:e4029 pubmed publisher..These findings suggest that modulating miR-221/222 levels may have a therapeutic potential in prostate carcinoma. ..
- Zheng C, Yinghao S, Li J. MiR-221 expression affects invasion potential of human prostate carcinoma cell lines by targeting DVL2. Med Oncol. 2012;29:815-22 pubmed publisher..We also suggest that miR-221 may control the migration of AIPC cells through DVL2, working as a key regulator in advanced CaP. The role of miR-221 in other target mRNA needs to be further investigated. ..
- Kang S, Ha Y, Kim S, Kang S, Park H, Lee J, et al. Do microRNA 96, 145 and 221 expressions really aid in the prognosis of prostate carcinoma?. Asian J Androl. 2012;14:752-7 pubmed publisher..To utilize miRNA as a diagnostic tool in clinical practice, more research is needed to understand miRNA mechanisms, identify miRNA targets, and further characterize miRNA function. ..
- Sun T, Wang Q, Balk S, Brown M, Lee G, Kantoff P. The role of microRNA-221 and microRNA-222 in androgen-independent prostate cancer cell lines. Cancer Res. 2009;69:3356-63 pubmed publisher..In conclusion, our data suggest the involvement of miR-221 and miR-222 in the development or maintenance of the CRPC phenotype. ..
- Wurz K, Garcia R, Goff B, Mitchell P, Lee J, Tewari M, et al. MiR-221 and MiR-222 alterations in sporadic ovarian carcinoma: Relationship to CDKN1B, CDKNIC and overall survival. Genes Chromosomes Cancer. 2010;49:577-84 pubmed publisher..01). In contrast, CDKN1B expression was not associated with miR-221 or miR-222 expression. Neither somatic mutations nor methylation of the studied region explained the alterations in miR-221 and miR-222 expression in most carcinomas. ..
- Mardente S, Mari E, Consorti F, Di Gioia C, Negri R, Etna M, et al. HMGB1 induces the overexpression of miR-222 and miR-221 and increases growth and motility in papillary thyroid cancer cells. Oncol Rep. 2012;28:2285-9 pubmed publisher..The overexpression of oncogenic miR-221 and miR-222 caused by HMGB1 is associated with an increase in malignancy scores, namely cell growth and motility. ..
- Hao J, Zhang C, Zhang A, Wang K, Jia Z, Wang G, et al. miR-221/222 is the regulator of Cx43 expression in human glioblastoma cells. Oncol Rep. 2012;27:1504-10 pubmed publisher..We conclude that miR-221/222 function as oncogenic microRNAs in human gliomas, at least in part, by targeting Cx43. ..
- Quintavalle C, Mangani D, Roscigno G, Romano G, Díaz Lagares A, Iaboni M, et al. MiR-221/222 target the DNA methyltransferase MGMT in glioma cells. PLoS ONE. 2013;8:e74466 pubmed publisher..Thus, chronic miR-221/222-mediated MGMT downregulation may render cells unable to repair genetic damage. This, associated also to miR-221/222 oncogenic potential, may poor GBM prognosis. ..
- Gillies J, Lorimer I. Regulation of p27Kip1 by miRNA 221/222 in glioblastoma. Cell Cycle. 2007;6:2005-9 pubmed..These data show that p27(Kip1) is a direct target for microRNAs 221 and 222, and suggest a role for these microRNAs in promoting the aggressive growth of human glioblastoma. ..
- Acunzo M, Visone R, Romano G, Veronese A, Lovat F, Palmieri D, et al. miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222. Oncogene. 2012;31:634-42 pubmed publisher..Moreover, we found that miR-130a reduced migratory capacity of NSCLC. A better understanding of MET-miR-221 and 222 axis regulation in drug resistance is the key in developing new strategies in NSCLC therapy. ..
- Spahn M, Kneitz S, Scholz C, Stenger N, Rudiger T, Strobel P, et al. Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrence. Int J Cancer. 2010;127:394-403 pubmed publisher..Our results showed that progressive miR-221 downregulation hallmarks metastasis and presents a novel prognostic marker in high risk PCa. This suggests that miR-221 has potential as a diagnostic marker and therapeutic target in PCa. ..
- Zhang C, Zhang J, Zhang A, Shi Z, Han L, Jia Z, et al. MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma. Mol Cancer. 2010;9:229 pubmed publisher..To our knowledge, these data indicate for the first time that miR-221/222 directly regulate apoptosis by targeting PUMA in glioblastoma and that miR-221/222 could be potential therapeutic targets for glioblastoma intervention. ..
- Mayoral R, Pipkin M, Pachkov M, van Nimwegen E, Rao A, Monticelli S. MicroRNA-221-222 regulate the cell cycle in mast cells. J Immunol. 2009;182:433-45 pubmed..Our study provides further insights on miR-221-222 transcriptional regulation as well as evidences that miR-221-222 regulate cell cycle checkpoints in mast cells in response to acute activation stimuli. ..
- Sun X, Liu B, Zhao X, Wang L, Ji W. MicroRNA-221 accelerates the proliferation of laryngeal cancer cell line Hep-2 by suppressing Apaf-1. Oncol Rep. 2015;33:1221-6 pubmed publisher..In conclusion, our results showed that miR-221 inhibition caused elevated expression levels of the Apaf-1 apoptotic pathway proteins caspase-3, -8 and -9. miR-221 may therefore be used as a novel therapeutic target for laryngeal cancer. ..
- Xuan H, Xue W, Pan J, Sha J, Dong B, Huang Y. Downregulation of miR-221, -30d, and -15a contributes to pathogenesis of prostate cancer by targeting Bmi-1. Biochemistry (Mosc). 2015;80:276-83 pubmed publisher..These results indicate that miR-221 and miR-30d are candidate tumor suppressor miRNAs in prostate cancer and therefore serve as potential clinical classification markers and therapeutic targets for human prostate cancer. ..