MiR-21: a Small Multi-faceted RNA

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2009 Jan 30

PMID 19175699

Citations 503

Authors

Anna M Krichevsky

Galina Gabriely

Affiliations

Soon will be listed here.

Abstract

More than 1000 microRNAs (miRNAs) are expressed in human cells, some tissue or cell type specific, others considered as house-keeping molecules. Functions and direct mRNA targets for some miRNAs have been relatively well studied over the last years. Every miRNA potentially regulates the expression of numerous protein-coding genes (tens to hundreds), but it has become increasingly clear that not all miRNAs are equally important; diverse high-throughput screenings of various systems have identified a limited number of key functional miRNAs over and over again. Particular miRNAs emerge as principal regulators that control major cell functions in various physiological and pathophysiological settings. Since its identification 3 years ago as the miRNA most commonly and strongly up-regulated in human brain tumour glioblastoma [1], miR-21 has attracted the attention of researchers in various fields, such as development, oncology, stem cell biology and aging, becoming one of the most studied miRNAs, along with let-7, miR-17-92 cluster ('oncomir-1'), miR-155 and a few others. However, an miR-21 knockout mouse has not yet been generated, and the data about miR-21 functions in normal cells are still very limited. In this review, we summarise the current knowledge of miR-21 functions in human disease, with an emphasis on its regulation, oncogenic role, targets in human cancers, potential as a disease biomarker and novel therapeutic target in oncology.

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References

Roversi G, Pfundt R, Moroni R, Magnani I, van Reijmersdal S, Pollo B . Identification of novel genomic markers related to progression to glioblastoma through genomic profiling of 25 primary glioma cell lines. Oncogene. 2005; 25(10):1571-83. DOI: 10.1038/sj.onc.1209177. View

Tran N, McLean T, Zhang X, Zhao C, Thomson J, OBrien C . MicroRNA expression profiles in head and neck cancer cell lines. Biochem Biophys Res Commun. 2007; 358(1):12-7. DOI: 10.1016/j.bbrc.2007.03.201. View

Krek A, Grun D, Poy M, Wolf R, Rosenberg L, Epstein E . Combinatorial microRNA target predictions. Nat Genet. 2005; 37(5):495-500. DOI: 10.1038/ng1536. View

Hu S, Ren G, Liu J, Zhao Z, Yu Y, Su R . MicroRNA expression and regulation in mouse uterus during embryo implantation. J Biol Chem. 2008; 283(34):23473-84. DOI: 10.1074/jbc.M800406200. View

Skog J, Wurdinger T, van Rijn S, Meijer D, Gainche L, Sena-Esteves M . Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008; 10(12):1470-6. PMC: 3423894. DOI: 10.1038/ncb1800. View

Thomson J, Newman M, Parker J, Morin-Kensicki E, Wright T, Hammond S . Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev. 2006; 20(16):2202-7. PMC: 1553203. DOI: 10.1101/gad.1444406. View

Johnson C, Huang Y, Parrish A, Smith M, Vaughn A, Zhang Q . Differential Apaf-1 levels allow cytochrome c to induce apoptosis in brain tumors but not in normal neural tissues. Proc Natl Acad Sci U S A. 2007; 104(52):20820-5. PMC: 2409225. DOI: 10.1073/pnas.0709101105. View

Cmarik J, Min H, Hegamyer G, Zhan S, Kulesz-Martin M, Yoshinaga H . Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation. Proc Natl Acad Sci U S A. 1999; 96(24):14037-42. PMC: 24186. DOI: 10.1073/pnas.96.24.14037. View

Clark J, Thomas D, Choong P, Dass C . RECK--a newly discovered inhibitor of metastasis with prognostic significance in multiple forms of cancer. Cancer Metastasis Rev. 2007; 26(3-4):675-83. DOI: 10.1007/s10555-007-9093-8. View

10.

Iorio M, Ferracin M, Liu C, Veronese A, Spizzo R, Sabbioni S . MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005; 65(16):7065-70. DOI: 10.1158/0008-5472.CAN-05-1783. View

11.

Keller S, Sanderson M, Stoeck A, Altevogt P . Exosomes: from biogenesis and secretion to biological function. Immunol Lett. 2006; 107(2):102-8. DOI: 10.1016/j.imlet.2006.09.005. View

12.

Johnson R, Zuccato C, Belyaev N, Guest D, Cattaneo E, Buckley N . A microRNA-based gene dysregulation pathway in Huntington's disease. Neurobiol Dis. 2007; 29(3):438-45. DOI: 10.1016/j.nbd.2007.11.001. View

13.

Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C . let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007; 131(6):1109-23. DOI: 10.1016/j.cell.2007.10.054. View

14.

Bitomsky N, Bohm M, Klempnauer K . Transformation suppressor protein Pdcd4 interferes with JNK-mediated phosphorylation of c-Jun and recruitment of the coactivator p300 by c-Jun. Oncogene. 2004; 23(45):7484-93. DOI: 10.1038/sj.onc.1208064. View

15.

Mudduluru G, Medved F, Grobholz R, Jost C, Gruber A, Leupold J . Loss of programmed cell death 4 expression marks adenoma-carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer. Cancer. 2007; 110(8):1697-707. DOI: 10.1002/cncr.22983. View

16.

Lankat-Buttgereit B, Gregel C, Knolle A, Hasilik A, Arnold R, Goke R . Pdcd4 inhibits growth of tumor cells by suppression of carbonic anhydrase type II. Mol Cell Endocrinol. 2004; 214(1-2):149-53. DOI: 10.1016/j.mce.2003.10.058. View

17.

Goke R, Barth P, Schmidt A, Samans B, Lankat-Buttgereit B . Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21(Waf1/Cip1). Am J Physiol Cell Physiol. 2004; 287(6):C1541-6. DOI: 10.1152/ajpcell.00025.2004. View

18.

Nam E, Yoon H, Kim S, Kim H, Kim Y, Kim J . MicroRNA expression profiles in serous ovarian carcinoma. Clin Cancer Res. 2008; 14(9):2690-5. DOI: 10.1158/1078-0432.CCR-07-1731. View

19.

Grimson A, Farh K, Johnston W, Garrett-Engele P, Lim L, Bartel D . MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell. 2007; 27(1):91-105. PMC: 3800283. DOI: 10.1016/j.molcel.2007.06.017. View

20.

Griffin C, Hawkins A, Packer R, RORKE L, Emanuel B . Chromosome abnormalities in pediatric brain tumors. Cancer Res. 1988; 48(1):175-80. View