Potential uses of microRNA in lung cancer diagnosis, prognosis, and therapy.

Lung cancer is the leading cause of death from cancer in the world. Although the molecular network of lung carcinogenesis has been partly known at the levels of genes and proteins, and personalized therapy based on the genetic changes has made considerable progress in the last decade, the high mortality rate is not markedly changed. MicroRNAs (miRNAs), a class of short endogenous RNAs, acting as post-transcriptional regulators of gene expression, are similar with siRNAs in both the biosynthesis and the function steps. While, miRNAs mostly silence gene expression by binding imperfectly matched sequences in the 3' UTR of target mRNA, which is different with siRNAs by targeting ORF of mRNA with a perfectly complementary manner. miRNAs have multiple functions in lung development, and abnormal expression of miRNAs could lead to lung tumorigenesis. The different expression profiles of miRNAs in lung cancer, and the stability of miRNAs in serum, all together make them as new potentially clinical biomarkers for diagnosis and prognosis. Moreover, miRNAs may serve as either novel potential targets acting directly as oncogenes (e.g. miR-17-92 cluster) or directly therapeutic molecules working as tumor suppressor genes (e.g. let-7 family). RNAi technology based on miRNAs has many advantages over siRNAs, such as in vivo stability, highly RNA promoter-compatibility and no overt toxicity. Eventually, it might overcome the present disadvantages and become a good candidate for lung cancer therapy.

[1]  Michael Z Michael,et al.  Reduced accumulation of specific microRNAs in colorectal neoplasia. , 2003, Molecular cancer research : MCR.

[2]  E. Izaurralde,et al.  P bodies: at the crossroads of post-transcriptional pathways , 2007, Nature Reviews Molecular Cell Biology.

[3]  Masato Nagino,et al.  let-7 regulates Dicer expression and constitutes a negative feedback loop. , 2008, Carcinogenesis.

[4]  Chun Xing Li,et al.  Differential expression of components of the microRNA machinery during mouse organogenesis. , 2005, Biochemical and biophysical research communications.

[5]  H. Tagawa,et al.  Synergistic action of the microRNA‐17 polycistron and Myc in aggressive cancer development , 2007, Cancer science.

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

[7]  S. Barik,et al.  Ectopic expression of miR-126*, an intronic product of the vascular endothelial EGF-like 7 gene, regulates prostein translation and invasiveness of prostate cancer LNCaP cells , 2008, Journal of Molecular Medicine.

[8]  J. Lieberman,et al.  let-7 Regulates Self Renewal and Tumorigenicity of Breast Cancer Cells , 2007, Cell.

[9]  X. Chen,et al.  Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases , 2008, Cell Research.

[10]  Imran Babar,et al.  MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. , 2007, Cancer research.

[11]  Stefano Volinia,et al.  MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  K. Ghoshal,et al.  Downregulation of miR‐122 in the rodent and human hepatocellular carcinomas , 2006, Journal of cellular biochemistry.

[13]  A. Burny,et al.  Evolution of microRNA expression during human bronchial squamous carcinogenesis , 2008, European Respiratory Journal.

[14]  Mark M Perry,et al.  Maternally imprinted microRNAs are differentially expressed during mouse and human lung development , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[15]  V. Ambros,et al.  Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation , 2004, Genome Biology.

[16]  B. Séraphin,et al.  Cytoplasmic foci are sites of mRNA decay in human cells , 2004, The Journal of cell biology.

[17]  L. O’Driscoll Current Cancer Drug Targets , 2009 .

[18]  F. Slack,et al.  RAS Is Regulated by the let-7 MicroRNA Family , 2005, Cell.

[19]  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.

[20]  F. Slack,et al.  The let-7 microRNA reduces tumor growth in mouse models of lung cancer , 2008, Cell cycle.

[21]  M. Oshimura,et al.  Dicer is essential for formation of the heterochromatin structure in vertebrate cells , 2004, Nature Cell Biology.

[22]  D. Bartel,et al.  MicroRNA-Directed Cleavage of HOXB8 mRNA , 2004, Science.

[23]  E. Zucca,et al.  Concomitant MYC and microRNA cluster miR-17-92 (C13orf25) amplification in human mantle cell lymphoma , 2007, Leukemia & lymphoma.

[24]  S. Elledge,et al.  Dicer is essential for mouse development , 2003, Nature Genetics.

[25]  C. Croce,et al.  miR-15 and miR-16 induce apoptosis by targeting BCL2. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Isabelle Behm-Ansmant,et al.  A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing. , 2005, RNA.

[27]  L. Chung,et al.  Primary adenocarcinomas of the lung in nonsmokers show a distinct pattern of allelic imbalance. , 2002, Cancer research.

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

[29]  E. Chan,et al.  Disruption of GW bodies impairs mammalian RNA interference , 2005, Nature Cell Biology.

[30]  Y. Ishikawa,et al.  let-7 microRNA expression is reduced in bronchioloalveolar carcinoma, a non-invasive carcinoma, and is not correlated with prognosis. , 2007, Lung cancer.

[31]  F. Slack,et al.  The let-7 microRNA represses cell proliferation pathways in human cells. , 2007, Cancer research.

[32]  Akira Ishizuka,et al.  Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways. , 2004, Genes & development.

[33]  F. Slack,et al.  The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. , 2000, Molecular cell.

[34]  J. M. Thomson,et al.  Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. , 2007, Developmental biology.

[35]  H. Horvitz,et al.  Heterochronic mutants of the nematode Caenorhabditis elegans. , 1984, Science.

[36]  S. Hwang,et al.  Altered MicroRNA Expression in Cervical Carcinomas , 2008, Clinical Cancer Research.

[37]  W. Gerald,et al.  Endogenous human microRNAs that suppress breast cancer metastasis , 2008, Nature.

[38]  Shingo Takagi,et al.  MicroRNA regulates the expression of human cytochrome P450 1B1. , 2006, Cancer research.

[39]  Erik J. Sontheimer,et al.  Assembly and function of RNA silencing complexes , 2005, Nature Reviews Molecular Cell Biology.

[40]  Chang-Zheng Chen,et al.  MicroRNAs as oncogenes and tumor suppressors. , 2005, The New England journal of medicine.

[41]  M. Lacey,et al.  MicroRNA-155 Is an Epstein-Barr Virus-Induced Gene That Modulates Epstein-Barr Virus-Regulated Gene Expression Pathways , 2008, Journal of Virology.

[42]  Ladan Fazli,et al.  Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development , 2007, Proceedings of the National Academy of Sciences.

[43]  C. Croce,et al.  MiR-15a and miR-16-1 cluster functions in human leukemia , 2008, Proceedings of the National Academy of Sciences.

[44]  Joshua T. Mendell,et al.  MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1 , 2008, Proceedings of the National Academy of Sciences.

[45]  Agnieszka Bronisz,et al.  Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. , 2008, Cancer research.

[46]  D. Bartel,et al.  Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. , 2005, RNA.

[47]  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.

[48]  T Takahashi,et al.  Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92 , 2007, Oncogene.

[49]  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.

[50]  Minchen Chien,et al.  Prognostic Values of microRNAs in Colorectal Cancer , 2006, Biomarker insights.

[51]  John W M Martens,et al.  Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer , 2008, Proceedings of the National Academy of Sciences.

[52]  J. M. Thomson,et al.  Direct Regulation of an Oncogenic Micro-RNA Cluster by E2F Transcription Factors* , 2007, Journal of Biological Chemistry.

[53]  Yan Zeng,et al.  Differential expression of microRNAs in early-stage neoplastic transformation in the lungs of F344 rats chronically treated with the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. , 2008, Carcinogenesis.

[54]  V. Kim MicroRNA biogenesis: coordinated cropping and dicing , 2005, Nature Reviews Molecular Cell Biology.

[55]  Muller Fabbri,et al.  A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. , 2005, The New England journal of medicine.

[56]  J. Yates,et al.  A role for the P-body component GW182 in microRNA function , 2005, Nature Cell Biology.

[57]  V. Kim,et al.  The nuclear RNase III Drosha initiates microRNA processing , 2003, Nature.

[58]  Mark M Perry,et al.  microRNA expression in the aging mouse lung , 2007, BMC Genomics.

[59]  E. Furth,et al.  Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster , 2006, Nature Genetics.

[60]  Annick Harel-Bellan,et al.  The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation , 2006, Nature Cell Biology.

[61]  Takashi Takahashi,et al.  Loss of heterozygosity (LOH) at 17q and 14q in human lung cancers , 1998, Oncogene.

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

[63]  C. Burge,et al.  Prediction of Mammalian MicroRNA Targets , 2003, Cell.

[64]  R. Quigg,et al.  miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130 , 2008, Proceedings of the National Academy of Sciences.

[65]  D. Bartel,et al.  Intronic microRNA precursors that bypass Drosha processing , 2007, Nature.

[66]  H. Blau,et al.  Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies , 2005, Nature Cell Biology.

[67]  S. Varambally,et al.  Genomic Loss of microRNA-101 Leads to Overexpression of Histone Methyltransferase EZH2 in Cancer , 2008, Science.

[68]  The STATus of miR-21 in apoptosis , 2007 .

[69]  Christopher P Evans,et al.  An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells , 2007, Proceedings of the National Academy of Sciences.

[70]  O. Maes,et al.  Murine microRNAs implicated in liver functions and aging process , 2008, Mechanisms of Ageing and Development.

[71]  Reuven Agami,et al.  miR-148 targets human DNMT3b protein coding region. , 2008, RNA.

[72]  T. Wurdinger,et al.  MiR-21 Promotes Glioma Invasion by Targeting MMP Regulators. , 2008 .

[73]  S. Lowe,et al.  A microRNA polycistron as a potential human oncogene , 2005, Nature.

[74]  B. Cullen,et al.  Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. , 2003, Genes & development.

[75]  E. Kistner,et al.  Let-7 expression defines two differentiation stages of cancer , 2007, Proceedings of the National Academy of Sciences.

[76]  Kaleb M. Pauley,et al.  Formation of GW bodies is a consequence of microRNA genesis , 2006, EMBO reports.

[77]  Vincent De Guire,et al.  An E2F/miR-20a Autoregulatory Feedback Loop* , 2007, Journal of Biological Chemistry.

[78]  Jing Wang,et al.  Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes , 2008, Nature Immunology.

[79]  Shuomin Zhu,et al.  MicroRNA-21 targets tumor suppressor genes in invasion and metastasis , 2008, Cell Research.

[80]  G. Ruvkun,et al.  A uniform system for microRNA annotation. , 2003, RNA.

[81]  B. Séraphin,et al.  The GW182 protein colocalizes with mRNA degradation associated proteins hDcp1 and hLSm4 in cytoplasmic GW bodies. , 2003, RNA.

[82]  R. Stephens,et al.  Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. , 2006, Cancer cell.

[83]  David P. Bartel,et al.  Supporting Online Material Materials and Methods Fig. S1 Tables S1 and S2 References Database S1 Disrupting the Pairing between Let-7 and Hmga2 Enhances Oncogenic Transformation , 2022 .

[84]  R. A. Robinson,et al.  Lung cancer histologic type in the surveillance, epidemiology, and end results registry versus independent review. , 2004, Journal of the National Cancer Institute.

[85]  Haoming Zhang,et al.  miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes , 2008, Nucleic acids research.

[86]  Min Han,et al.  The developmental timing regulator AIN-1 interacts with miRISCs and may target the argonaute protein ALG-1 to cytoplasmic P bodies in C. elegans. , 2005, Molecular cell.

[87]  T. Wurdinger,et al.  MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators , 2008, Molecular and Cellular Biology.

[88]  T. Golub,et al.  Impaired microRNA processing enhances cellular transformation and tumorigenesis , 2007, Nature Genetics.

[89]  Rudolf Jaenisch,et al.  Targeted Deletion Reveals Essential and Overlapping Functions of the miR-17∼92 Family of miRNA Clusters , 2008, Cell.

[90]  George A. Calin,et al.  A MicroRNA Signature of Hypoxia , 2006, Molecular and Cellular Biology.

[91]  Stephen Safe,et al.  The oncogenic microRNA-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. , 2007, Cancer research.

[92]  Yun Lu,et al.  Epithelial progenitor cells of the embryonic lung and the role of microRNAs in their proliferation. , 2008, Proceedings of the American Thoracic Society.

[93]  B. Reinhart,et al.  Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA , 2000, Nature.

[94]  Tara L. Naylor,et al.  microRNAs exhibit high frequency genomic alterations in human cancer. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[95]  Rajiv Dhir,et al.  Up-regulation of dicer, a component of the MicroRNA machinery, in prostate adenocarcinoma. , 2006, The American journal of pathology.

[96]  D. Katsaros,et al.  Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-II expression and favorable prognosis. , 2007, Cancer research.

[97]  H. Sültmann,et al.  The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function. , 2007, Cancer research.

[98]  Manfred Kunz,et al.  MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth , 2008, Cell Research.

[99]  Aadel A. Chaudhuri,et al.  Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder , 2008, The Journal of experimental medicine.

[100]  Ola Snøve,et al.  Distance constraints between microRNA target sites dictate efficacy and cooperativity , 2007, Nucleic acids research.

[101]  Stefanie Dimmeler,et al.  Role of Dicer and Drosha for Endothelial MicroRNA Expression and Angiogenesis , 2007, Circulation research.

[102]  Anwar Hossain,et al.  Mir-17-5p Regulates Breast Cancer Cell Proliferation by Inhibiting Translation of AIB1 mRNA , 2006, Molecular and Cellular Biology.

[103]  本山 一夫 Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family , 2009 .

[104]  R. Xie,et al.  MicroRNA expression profile of bronchioalveolar stem cells from mouse lung. , 2008, Biochemical and biophysical research communications.

[105]  Patricia Soteropoulos,et al.  MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. , 2007, Cancer research.

[106]  A. Fire,et al.  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans , 1998, Nature.

[107]  S. Landais,et al.  Oncogenic potential of the miR-106-363 cluster and its implication in human T-cell leukemia. , 2007, Cancer research.

[108]  Fang Zhou,et al.  Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. , 2008, Cancer research.

[109]  Wayne Tam,et al.  Accumulation of miR-155 and BIC RNA in human B cell lymphomas. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[110]  Vassilis Georgoulias,et al.  Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR. , 2008, Clinical chemistry.

[111]  R. Sachidanandam,et al.  A role for microRNAs in maintenance of mouse mammary epithelial progenitor cells , 2007 .

[112]  Rudolf Jaenisch,et al.  DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal , 2007, Nature Genetics.

[113]  Ji Young Kim,et al.  MicroRNA miR-199a* Regulates the MET Proto-oncogene and the Downstream Extracellular Signal-regulated Kinase 2 (ERK2)* , 2008, Journal of Biological Chemistry.

[114]  Michael T. McManus,et al.  Conditional Loss of Dicer Disrupts Cellular and Tissue Morphogenesis in the Cortex and Hippocampus , 2008, The Journal of Neuroscience.

[115]  Y. Yatabe,et al.  A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. , 2005, Cancer research.

[116]  W. Hauswirth,et al.  Dicer Inactivation Leads to Progressive Functional and Structural Degeneration of the Mouse Retina , 2008, The Journal of Neuroscience.

[117]  William Ignace Wei,et al.  Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue , 2008, Clinical Cancer Research.

[118]  Michael T. McManus,et al.  Essential role for Dicer during skeletal muscle development. , 2007, Developmental biology.

[119]  S. Jayasena,et al.  Functional siRNAs and miRNAs Exhibit Strand Bias , 2003, Cell.

[120]  O. Kent,et al.  A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes , 2006, Oncogene.

[121]  K. Jeang,et al.  Roles for microRNAs, miR-93 and miR-130b, and tumor protein 53-induced nuclear protein 1 tumor suppressor in cell growth dysregulation by human T-cell lymphotrophic virus 1. , 2008, Cancer research.

[122]  Hiroyuki Tagawa,et al.  Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. , 2004, Cancer research.

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

[124]  Kiyoshi Asai,et al.  Characterization of endogenous human Argonautes and their miRNA partners in RNA silencing , 2008, Proceedings of the National Academy of Sciences.

[125]  J. M. Thomson,et al.  Argonaute2 Is the Catalytic Engine of Mammalian RNAi , 2004, Science.

[126]  Erik Flemington,et al.  B-cell Receptor Activation Induces BIC/miR-155 Expression through a Conserved AP-1 Element* , 2008, Journal of Biological Chemistry.

[127]  K. Jöckel,et al.  Diagnostic agreement in the histopathological evaluation of lung cancer tissue in a population-based case-control study. , 2006, Lung cancer.

[128]  Heidi J. Peltier,et al.  Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues. , 2008, RNA.

[129]  W. Tam,et al.  miR‐155/BIC as an oncogenic microRNA , 2006, Genes, chromosomes & cancer.

[130]  Phillip A Sharp,et al.  Suppression of non-small cell lung tumor development by the let-7 microRNA family , 2008, Proceedings of the National Academy of Sciences.

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

[132]  Michael T. McManus,et al.  The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[133]  Simion I. Chiosea,et al.  Overexpression of Dicer in precursor lesions of lung adenocarcinoma. , 2007, Cancer research.

[134]  Yariv Yogev,et al.  Serum MicroRNAs Are Promising Novel Biomarkers , 2008, PloS one.

[135]  F. Saggioro,et al.  MicroRNAs differentially expressed in ACTH-secreting pituitary tumors. , 2009, The Journal of clinical endocrinology and metabolism.

[136]  Pedro J. Batista,et al.  Analysis of the C. elegans Argonaute Family Reveals that Distinct Argonautes Act Sequentially during RNAi , 2006, Cell.

[137]  F. Hirsch,et al.  EGFR regulation by microRNA in lung cancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[138]  Daniel B. Martin,et al.  Circulating microRNAs as stable blood-based markers for cancer detection , 2008, Proceedings of the National Academy of Sciences.

[139]  Anindya Dutta,et al.  The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. , 2007, Genes & development.

[140]  G. Nuovo,et al.  MicroRNA-126 inhibits invasion in non-small cell lung carcinoma cell lines. , 2008, Biochemical and biophysical research communications.

[141]  Jinhong Chang,et al.  Liver-Specific MicroRNA miR-122 Enhances the Replication of Hepatitis C Virus in Nonhepatic Cells , 2008, Journal of Virology.

[142]  S. Lippman,et al.  Molecular signatures of lung cancer--toward personalized therapy. , 2007, The New England journal of medicine.

[143]  H. Leffers,et al.  Translational repression of E2F1 mRNA in carcinoma in situ and normal testis correlates with expression of the miR-17-92 cluster , 2007, Cell Death and Differentiation.

[144]  C. Roussos,et al.  Cytogenetic and molecular aspects of lung cancer. , 2006, Cancer letters.

[145]  George A Calin,et al.  Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[146]  N. Colburn,et al.  MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene , 2008, Oncogene.

[147]  L. Lim,et al.  MicroRNAs in the miR-106b Family Regulate p21/CDKN1A and Promote Cell Cycle Progression , 2008, Molecular and Cellular Biology.

[148]  Gregory J. Hannon,et al.  microRNAs join the p53 network — another piece in the tumour-suppression puzzle , 2007, Nature Reviews Cancer.

[149]  Carme Camps,et al.  hsa-miR-210 Is Induced by Hypoxia and Is an Independent Prognostic Factor in Breast Cancer , 2008, Clinical Cancer Research.

[150]  A. Krogh,et al.  Programmed Cell Death 4 (PDCD4) Is an Important Functional Target of the MicroRNA miR-21 in Breast Cancer Cells* , 2008, Journal of Biological Chemistry.

[151]  C. Burge,et al.  Identification of let-7-regulated oncofetal genes. , 2008, Cancer research.

[152]  Michael T. McManus,et al.  Dicer function is essential for lung epithelium morphogenesis , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[153]  T. Davison,et al.  MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma , 2007, Oncogene.

[154]  V. Kim,et al.  MicroRNA maturation: stepwise processing and subcellular localization , 2002, The EMBO journal.

[155]  Huan Yang,et al.  MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. , 2008, Cancer research.

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

[157]  Michaela Scherr,et al.  MicroRNA and lung cancer. , 2005, The New England journal of medicine.

[158]  George A Calin,et al.  Micro-RNA profiling in kidney and bladder cancers. , 2007, Urologic oncology.

[159]  D. Dykxhoorn,et al.  Killing the messenger: short RNAs that silence gene expression , 2003, Nature Reviews Molecular Cell Biology.

[160]  J. Pollack,et al.  MYC stimulates EZH2 expression by repression of its negative regulator miR-26a. , 2008, Blood.

[161]  Y. Yatabe,et al.  Reduced Expression of the let-7 MicroRNAs in Human Lung Cancers in Association with Shortened Postoperative Survival , 2004, Cancer Research.

[162]  C. Croce,et al.  MicroRNA signatures in human cancers , 2006, Nature Reviews Cancer.

[163]  A. Aigner Gene silencing through RNA interference (RNAi) in vivo: strategies based on the direct application of siRNAs. , 2006, Journal of biotechnology.

[164]  Isabelle Behm-Ansmant,et al.  P-Body Formation Is a Consequence, Not the Cause, of RNA-Mediated Gene Silencing , 2007, Molecular and Cellular Biology.

[165]  Shuomin Zhu,et al.  MicroRNA-21 Targets the Tumor Suppressor Gene Tropomyosin 1 (TPM1)* , 2007, Journal of Biological Chemistry.

[166]  S. Knuutila,et al.  Increased expression of high mobility group A proteins in lung cancer , 2006, The Journal of pathology.

[167]  T. Rana,et al.  Translation Repression in Human Cells by MicroRNA-Induced Gene Silencing Requires RCK/p54 , 2006, PLoS biology.

[168]  George E. Sandusky,et al.  Dicer Is Required for Embryonic Angiogenesis during Mouse Development* , 2005, Journal of Biological Chemistry.

[169]  C. Croce,et al.  MicroRNA gene expression deregulation in human breast cancer. , 2005, Cancer research.

[170]  Y. Diao,et al.  The design of vectors for RNAi delivery system. , 2008, Current pharmaceutical design.

[171]  Lin Liu,et al.  Identification of rat lung-specific microRNAs by micoRNA microarray: valuable discoveries for the facilitation of lung research , 2007, BMC Genomics.

[172]  Yukio Kitade,et al.  Downregulation of microRNAs‐143 and ‐145 in B‐cell malignancies , 2007, Cancer science.

[173]  Fabio Martelli,et al.  MicroRNA-210 Modulates Endothelial Cell Response to Hypoxia and Inhibits the Receptor Tyrosine Kinase Ligand Ephrin-A3* , 2008, Journal of Biological Chemistry.

[174]  H. Inoue,et al.  Clinical Significance of HighMobility Group A 2 in Human Gastric Cancer and Its Relationship to let-7 , 2008 .

[175]  R. Vyzula,et al.  Altered Expression of miR-21, miR-31, miR-143 and miR-145 Is Related to Clinicopathologic Features of Colorectal Cancer , 2008, Oncology.

[176]  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.

[177]  Roy Parker,et al.  Decapping and Decay of Messenger RNA Occur in Cytoplasmic Processing Bodies , 2003 .

[178]  Shuta Tomida,et al.  Reduced expression of Dicer associated with poor prognosis in lung cancer patients , 2005, Cancer science.

[179]  Sung-Liang Yu,et al.  MicroRNA signature predicts survival and relapse in lung cancer. , 2008, Cancer cell.