MicroRNA and cancer--a brief overview.

MicroRNAs (miRNAs) are short non-coding RNAs with a length of ∼22 nucleotides, involved in posttranscriptional regulation of gene expression. Until now, over 2588 miRNAs have been identified in humans and the list is growing. MicroRNAs have an important role in all biological processes and aberrant miRNA expression is associated with many diseases including cancer. In the year 2002 the first connection between cancer and miRNA deregulation was discovered. Since then, a lot of information about the key role which miRNAs play in cancer development and drug resistance has been gained. However, there is still a long way to go to fully understand the miRNA world. In this review, we briefly describe miRNA biogenesis and discuss the role of miRNAs in cancer development and drug resistance. Finally we explain how miRNAs can be used as biomarkers and as a novel therapeutic approach in cancer.

[1]  J. Mendell,et al.  MicroRNAs in cell proliferation, cell death, and tumorigenesis , 2006, British Journal of Cancer.

[2]  C. Croce.  Causes and consequences of microRNA dysregulation in cancer , 2009, Nature Reviews Genetics.

[3]  Peter S Linsley,et al.  MicroRNAs and Cell Cycle Regulation , 2007, Cell cycle.

[4]  A. Lund,et al.  MicroRNA and cancer , 2012, Molecular oncology.

[5]  A. Yee,et al.  Correction: Versican G3 Domain Modulates Breast Cancer Cell Apoptosis: A Mechanism for Breast Cancer Cell Response to Chemotherapy and EGFR Therapy , 2012, PLoS ONE.

[6]  A. Bradley,et al.  Identification of mammalian microRNA host genes and transcription units. , 2004, Genome research.

[7]  Zhiguo Wang.  The guideline of the design and validation of MiRNA mimics. , 2011, Methods in molecular biology.

[8]  Bin Li,et al.  A miR-SNP of the XPO5 gene is associated with advanced non-small-cell lung cancer , 2013, OncoTargets and therapy.

[9]  K. Vickers,et al.  MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins , 2011, Nature Cell Biology.

[10]  M. Jovanović,et al.  miRNAs and apoptosis: RNAs to die for , 2006, Oncogene.

[11]  C. Croce,et al.  Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Mei Mei,et al.  Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status , 2010, Laboratory Investigation.

[13]  S. Tavazoie,et al.  A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells , 2011, Nature.

[14]  J. Lötvall,et al.  Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells , 2007, Nature Cell Biology.

[15]  Xiaolan Zhu,et al.  miR-126 enhances the sensitivity of non-small cell lung cancer cells to anticancer agents by targeting vascular endothelial growth factor A. , 2012, Acta Biochimica et Biophysica Sinica.

[16]  P. Pandolfi,et al.  Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis. , 2011, Cancer cell.

[17]  G. Ruvkun,et al.  Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans , 1993, Cell.

[18]  Sanghyuk Lee,et al.  MicroRNA genes are transcribed by RNA polymerase II , 2004, The EMBO journal.

[19]  M. Manzanares,et al.  MiRNA-mediated regulation of cell signaling and homeostasis in the early mouse embryo , 2011, Cell cycle.

[20]  Wei Wang,et al.  MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. , 2007, Cancer research.

[21]  N. Rajewsky,et al.  A pancreatic islet-specific microRNA regulates insulin secretion , 2004, Nature.

[22]  F. Slack,et al.  microRNA Control of Lifespan and Metabolism , 2006, Cell cycle.

[23]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[24]  F. Slack,et al.  OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma , 2010, Nature.

[25]  M. Esteller.  Epigenetics in cancer. , 2008, The New England journal of medicine.

[26]  C. Croce,et al.  A microRNA signature defines chemoresistance in ovarian cancer through modulation of angiogenesis , 2013, Proceedings of the National Academy of Sciences.

[27]  C. Croce,et al.  Cross-talk between MET and EGFR in non-small cell lung cancer involves miR-27a and Sprouty2 , 2013, Proceedings of the National Academy of Sciences.

[28]  C. Croce,et al.  MiR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non–small-cell lung cancer through BIM down-regulation , 2012, Proceedings of the National Academy of Sciences.

[29]  T. Tuschl,et al.  Identification of Novel Genes Coding for Small Expressed RNAs , 2001, Science.

[30]  Xiuping Liu,et al.  Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. , 2008, Biochemical pharmacology.

[31]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[32]  G. Calin,et al.  Clinical relevance of circulating cell-free microRNAs in cancer , 2014, Nature Reviews Clinical Oncology.

[33]  George A Calin,et al.  MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. , 2008, JAMA.

[34]  R. Hassan,et al.  miRNA-451: A putative predictor marker of Imatinib therapy response in chronic myeloid leukemia. , 2012, Leukemia research : a Forum for Studies on Leukemia and Normal Hemopoiesis.

[35]  M. Peter.  Regulating cancer stem cells the miR way. , 2010, Cell Stem Cell.

[36]  Nahum Sonenberg,et al.  The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC , 2012, Nature Structural &Molecular Biology.

[37]  L. Lim,et al.  A microRNA component of the p53 tumour suppressor network , 2007, Nature.

[38]  Ali Nahvi,et al.  A Parsimonious Model for Gene Regulation by miRNAs , 2011, Science.

[39]  Johan Hansson,et al.  MicroRNA expression profiles associated with mutational status and survival in malignant melanoma. , 2010, The Journal of investigative dermatology.

[40]  H. Ishii,et al.  Role of microRNAs in solid tumors , 2011 .

[41]  L. Lim,et al.  An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans , 2001, Science.

[42]  V. Kim,et al.  The Drosha-DGCR8 complex in primary microRNA processing. , 2004, Genes & development.

[43]  Woonyoung Choi,et al.  miR-200 Expression Regulates Epithelial-to-Mesenchymal Transition in Bladder Cancer Cells and Reverses Resistance to Epidermal Growth Factor Receptor Therapy , 2009, Clinical Cancer Research.

[44]  Jan-Fang Cheng,et al.  Dicer, Drosha, and outcomes in patients with ovarian cancer. , 2008, The New England journal of medicine.

[45]  A. Bader,et al.  Developing therapeutic microRNAs for cancer , 2011, Gene Therapy.

[46]  C. Croce,et al.  Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[47]  Ugo Boggi,et al.  MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. , 2010, Cancer research.

[48]  C. Croce,et al.  microRNA involvement in human cancer. , 2012, Carcinogenesis.

[49]  D. Kwong,et al.  MicroRNA-144 promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma through repression of PTEN. , 2013, Carcinogenesis.

[50]  C. Croce,et al.  MicroRNAs in Cancer. , 2009, Annual review of medicine.

[51]  M. Stoffel,et al.  Specificity, duplex degradation and subcellular localization of antagomirs , 2007, Nucleic acids research.

[52]  Xiaohua Li,et al.  Survival prediction of gastric cancer by a seven-microRNA signature , 2009, Gut.

[53]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[54]  Michael F. Clarke,et al.  Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells , 2009, Cell.

[55]  D. Brown,et al.  The promise of microRNA replacement therapy. , 2010, Cancer research.

[56]  V. Kim,et al.  MicroRNA precursors in motion: exportin-5 mediates their nuclear export. , 2004, Trends in cell biology.

[57]  V. Kim,et al.  Biogenesis of small RNAs in animals , 2009, Nature Reviews Molecular Cell Biology.

[58]  Jesse D. Ziebarth,et al.  Treatment- and Population-Dependent Activity Patterns of Behavioral and Expression QTLs , 2012, PloS one.

[59]  E. Kroh,et al.  Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma , 2011, Proceedings of the National Academy of Sciences.

[60]  C. Morrison,et al.  MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B , 2007, Proceedings of the National Academy of Sciences.

[61]  A. Tijsen,et al.  Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? , 2012, Circulation research.

[62]  Jianli Lu,et al.  Folding zones inside the ribosomal exit tunnel , 2005, Nature Structural &Molecular Biology.

[63]  Sidhartha Hazari,et al.  Increased expression of P-glycoprotein and doxorubicin chemoresistance of metastatic breast cancer is regulated by miR-298. , 2012, The American journal of pathology.

[64]  X. Yao,et al.  Involvement of microRNA-21 in mediating chemo-resistance to docetaxel in androgen-independent prostate cancer PC3 cells , 2010, Acta Pharmacologica Sinica.

[65]  S. Alahari,et al.  miRNA control of tumor cell invasion and metastasis , 2010, International journal of cancer.

[66]  Kathryn A. O’Donnell,et al.  c-Myc-regulated microRNAs modulate E2F1 expression , 2005, Nature.

[67]  S. Dimmeler,et al.  MicroRNAs and Stem Cells: Control of Pluripotency, Reprogramming, and Lineage Commitment , 2012, Circulation research.

[68]  C. Denkert,et al.  An illegitimate microRNA target site within the 3' UTR of MDM4 affects ovarian cancer progression and chemosensitivity. , 2010, Cancer research.

[69]  Burton B. Yang,et al.  Stress Response of Glioblastoma Cells Mediated by miR-17-5p Targeting PTEN and the Passenger Strand miR-17-3p Targeting MDM2 , 2012, Oncotarget.

[70]  P. Jin,et al.  RNA and microRNAs in fragile X mental retardation , 2004, Nature Cell Biology.

[71]  H. Horvitz,et al.  MicroRNA expression profiles classify human cancers , 2005, Nature.

[72]  Hansjuerg Alder,et al.  miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. , 2009, Cancer cell.

[73]  B. Harfe,et al.  MicroRNAs in vertebrate development. , 2005, Current opinion in genetics & development.

[74]  Peter A. Jones,et al.  Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. , 2006, Cancer cell.

[75]  Cicek Gercel-Taylor,et al.  MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. , 2008, Gynecologic oncology.

[76]  F. Slack,et al.  A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk. , 2008, Cancer research.

[77]  Stefano Volinia,et al.  MicroRNA Profiles Discriminate among Colon Cancer Metastasis , 2014, PloS one.

[78]  B. Reinhart,et al.  The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans , 2000, Nature.

[79]  Í. Lopes-Cendes,et al.  The new world of RNAs , 2013, Genetics and molecular biology.

[80]  C. Croce,et al.  miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222 , 2012, Oncogene.

[81]  Hyunsuk Shim,et al.  Regulation of miR-19 to Breast Cancer Chemoresistance Through Targeting PTEN , 2011, Pharmaceutical Research.

[82]  V. Ambros,et al.  An Extensive Class of Small RNAs in Caenorhabditis elegans , 2001, Science.

[83]  H. Xia,et al.  MicroRNA-214 regulates the acquired resistance to gefitinib via the PTEN/AKT pathway in EGFR-mutant cell lines. , 2012, Asian Pacific journal of cancer prevention : APJCP.

[84]  M. Fabbri,et al.  Epigenetic regulation of miRNAs in cancer. , 2013, Advances in experimental medicine and biology.

[85]  R. Shiekhattar,et al.  TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing , 2005, Nature.

[86]  S. Tavazoie,et al.  Control of metastatic progression by microRNA regulatory networks , 2013, Nature Cell Biology.

[87]  R. Aharonov,et al.  MicroRNAs accurately identify cancer tissue origin , 2008, Nature Biotechnology.

[88]  D. Bartel.  MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[89]  Douglas D. Taylor,et al.  Exosomal microRNA: a diagnostic marker for lung cancer. , 2008, Clinical lung cancer.

[90]  D. Haber,et al.  Dual Role for Argonautes in MicroRNA Processing and Posttranscriptional Regulation of MicroRNA Expression , 2007, Cell.

[91]  Li Zhou,et al.  Small RNAs have a large impact , 2012, RNA biology.

[92]  Dennis Shasha,et al.  miR-Synth: a computational resource for the design of multi-site multi-target synthetic miRNAs , 2014, Nucleic acids research.

[93]  A. Schetter,et al.  MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers , 2009, Proceedings of the National Academy of Sciences.

[94]  J Ma,et al.  MicroRNA and drug resistance , 2010, Cancer Gene Therapy.

[95]  Oscar F. Silvestre,et al.  A nanoparticle formula for delivering siRNA or miRNAs to tumor cells in cell culture and in vivo , 2014, Nature Protocols.

[96]  M. Hristov,et al.  Delivery of MicroRNA-126 by Apoptotic Bodies Induces CXCL12-Dependent Vascular Protection , 2009, Science Signaling.