Diverse roles of miR-29 in cancer (review).

microRNAs (miRNAs) are non-coding RNAs which have the capacity to regulate gene expression at the post-transcriptional level, and have emerging as key factors involved in cancer at all stages ranging from initiation to metastasis. In the present review, we summmarize the diverse roles of the microRNA-29 (miR-29) family in cancer. First, we present a concise introduction to the miR-29 family and the expression profile of miR-29 in various cancer types. We next highlight the upstream regulatory pathway of miR-29 and describe the relationship between miR-29 and cancer in detail. As a tumor suppressor, miR-29 restrains cancer progression by promoting tumor cell apoptosis, by suppressing DNA methylation of tumor-suppressor genes, by reducing proliferation of tumors and by increasing chemosensitivity. However, as a tumor promoter, miR-29 mediates epithelial-mesenchymal transition (EMT) and promotes metastasis in breast cancer and colon cancer. Finally, we suggest that miR-29 represents a novel diagnostic and prognostic biomarker or a therapeutic target for cancer. Our review highlights the diverse relationship between miR-29 and cancer (particularly digestive system neoplasms). Further research of miR-29 in cancer is warranted.

[1]  Paul Ahlquist,et al.  MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins , 2008, Proceedings of the National Academy of Sciences.

[2]  Pengfei Li,et al.  microRNA-29b contributes to pre-eclampsia through its effects on apoptosis, invasion and angiogenesis of trophoblast cells. , 2013, Clinical science.

[3]  C. Croce,et al.  MicroRNA 29b functions in acute myeloid leukemia. , 2009, Blood.

[4]  Jiabei Wang,et al.  microRNA expression alteration after arsenic trioxide treatment in HepG‐2 cells , 2011, Journal of gastroenterology and hepatology.

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

[6]  Zhaoyong Hu,et al.  Downregulation of microRNA-29 by antisense inhibitors and a PPAR-gamma agonist protects against myocardial ischaemia-reperfusion injury. , 2010, Cardiovascular research.

[7]  Torsten Haferlach,et al.  Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin , 2008, Proceedings of the National Academy of Sciences.

[8]  J. Yun,et al.  Effects of MicroRNA‐29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma , 2009, Hepatology.

[9]  Jing Ping Zhang,et al.  MicroRNA‐29b suppresses tumor angiogenesis, invasion, and metastasis by regulating matrix metalloproteinase 2 expression , 2011, Hepatology.

[10]  A. Levine,et al.  The p53 tumour suppressor gene , 1991, Nature.

[11]  C. Croce,et al.  MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome , 2009, Gut.

[12]  Huating Wang,et al.  NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. , 2008, Cancer cell.

[13]  V. Puduvalli,et al.  Histone deacetylases mediate the silencing of miR-15a, miR-16, and miR-29b in chronic lymphocytic leukemia. , 2012, Blood.

[14]  M. Vinciguerra,et al.  MicroRNA-29 in Aortic Dilation: Implications for Aneurysm Formation , 2011, Circulation research.

[15]  T. Luedde,et al.  Micro‐RNA profiling reveals a role for miR‐29 in human and murine liver fibrosis , 2011, Hepatology.

[16]  Kai Fu,et al.  Coordinated silencing of MYC-mediated miR-29 by HDAC3 and EZH2 as a therapeutic target of histone modification in aggressive B-Cell lymphomas. , 2012, Cancer cell.

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

[18]  Danqiong Sun,et al.  Metalloprotease-Disintegrin ADAM12 Expression Is Regulated by Notch Signaling via MicroRNA-29* , 2011, The Journal of Biological Chemistry.

[19]  J. Yates,et al.  Identification of Novel Targets for miR-29a Using miRNA Proteomics , 2012, PloS one.

[20]  Zhaoli Chen,et al.  miR-29c induces cell cycle arrest in esophageal squamous cell carcinoma by modulating cyclin E expression. , 2011, Carcinogenesis.

[21]  M. Zago,et al.  miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia. , 2007, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[22]  K. Junker,et al.  Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma , 2011, World Journal of Urology.

[23]  Takashi Suzuki,et al.  Changes in microRNA expression levels correlate with clinicopathological features and prognoses in endometrial serous adenocarcinomas , 2010, Cancer science.

[24]  Anke Wienecke-Baldacchino,et al.  Interferon-γ-induced activation of Signal Transducer and Activator of Transcription 1 (STAT1) up-regulates the tumor suppressing microRNA-29 family in melanoma cells , 2012, Cell Communication and Signaling.

[25]  Merlin C. Thomas,et al.  Suppression of microRNA-29 expression by TGF-β1 promotes collagen expression and renal fibrosis. , 2012, Journal of the American Society of Nephrology : JASN.

[26]  Y. Pekarsky,et al.  Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. , 2006, Cancer research.

[27]  Yanhong Zhou,et al.  Circulating miR-17, miR-20a, miR-29c, and miR-223 Combined as Non-Invasive Biomarkers in Nasopharyngeal Carcinoma , 2012, PloS one.

[28]  Oliver Distler,et al.  MicroRNA-29, a key regulator of collagen expression in systemic sclerosis. , 2010, Arthritis and rheumatism.

[29]  S. Bronk,et al.  Transcriptional suppression of mir‐29b‐1/mir‐29a promoter by c‐Myc, hedgehog, and NF‐kappaB , 2010, Journal of cellular biochemistry.

[30]  Zhiming Wang,et al.  miR-21 promotes migration and invasion by the miR-21-PDCD4-AP-1 feedback loop in human hepatocellular carcinoma. , 2012, Oncology reports.

[31]  Peng Ru,et al.  miRNA-29b Suppresses Prostate Cancer Metastasis by Regulating Epithelial–Mesenchymal Transition Signaling , 2012, Molecular Cancer Therapeutics.

[32]  T. Gambichler,et al.  Expression of microRNAs in basal cell carcinoma , 2012, The British journal of dermatology.

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

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

[35]  Ignacio Varela,et al.  Aging and chronic DNA damage response activate a regulatory pathway involving miR‐29 and p53 , 2011, The EMBO journal.

[36]  K. Zatloukal,et al.  miR‐29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis , 2009, EMBO reports.

[37]  Zuhong Lu,et al.  Analysis of serum genome-wide microRNAs for breast cancer detection. , 2012, Clinica chimica acta; international journal of clinical chemistry.

[38]  M. Tschan,et al.  MicroRNA-29b is involved in the Src-ID1 signaling pathway and is dysregulated in human lung adenocarcinoma , 2012, Oncogene.

[39]  Anne-Marie Cleton-Jansen,et al.  Modulation of the Osteosarcoma Expression Phenotype by MicroRNAs , 2012, PloS one.

[40]  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.

[41]  Jian-yong Li,et al.  Serum microRNAs are promising novel biomarkers for diffuse large B cell lymphoma , 2012, Annals of Hematology.

[42]  C. Bloomfield,et al.  MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. , 2009, Blood.

[43]  M. Henry,et al.  MiRNA-29a regulates the expression of numerous proteins and reduces the invasiveness and proliferation of human carcinoma cell lines. , 2009, European journal of cancer.

[44]  M. Caligiuri,et al.  Clinical and pharmacodynamic activity of bortezomib and decitabine in acute myeloid leukemia. , 2012, Blood.

[45]  C. Croce,et al.  Karyotype-specific microRNA signature in chronic lymphocytic leukemia. , 2009, Blood.

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

[47]  Jeffrey E. Thatcher,et al.  Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis , 2008, Proceedings of the National Academy of Sciences.

[48]  Hansjuerg Alder,et al.  The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. , 2009, Gynecologic oncology.

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

[50]  N. Rajewsky,et al.  The evolution of gene regulation by transcription factors and microRNAs , 2007, Nature Reviews Genetics.

[51]  Z. Werb,et al.  GATA3 suppresses metastasis and modulates the tumour microenvironment by regulating microRNA-29b expression , 2013, Nature Cell Biology.

[52]  Chen Wang,et al.  A combined approach identifies three mRNAs that are down-regulated by microRNA-29b and promote invasion ability in the breast cancer cell line MCF-7 , 2012, Journal of Cancer Research and Clinical Oncology.

[53]  Zhaohui Huang,et al.  Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer , 2010, International journal of cancer.

[54]  Hong Xu,et al.  MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3: potential implications for immune based therapy of human solid tumors. , 2009, Cancer research.

[55]  Laura A. Sullivan,et al.  Aberrant overexpression of IL-15 initiates large granular lymphocyte leukemia through chromosomal instability and DNA hypermethylation. , 2012, Cancer cell.

[56]  M. Mann,et al.  miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. , 2002, Genes & development.

[57]  Min Pan,et al.  A miRNA-regulatory network explains how dysregulated miRNAs perturb oncogenic processes across diverse cancers , 2012, Genome research.

[58]  C. Sander,et al.  A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing , 2007, Cell.

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

[60]  W. Zhang,et al.  The microRNA-29 plays a central role in osteosarcoma pathogenesis and progression , 2012, Molecular Biology.

[61]  R. Aharonov,et al.  Tumor microRNA-29a expression and the risk of recurrence in stage II colon cancer. , 2012, International journal of oncology.

[62]  Fang Wang,et al.  miR-29a and miR-142-3p downregulation and diagnostic implication in human acute myeloid leukemia , 2011, Molecular Biology Reports.

[63]  Zhao-dian Chen,et al.  Up-regulation of microRNA in bladder tumor tissue is not common , 2010, International Urology and Nephrology.

[64]  S. Le,et al.  Aberrant Expression of Oncogenic and Tumor-Suppressive MicroRNAs in Cervical Cancer Is Required for Cancer Cell Growth , 2008, PloS one.

[65]  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.

[66]  A. Jemal,et al.  Cancer statistics, 2012 , 2012, CA: a cancer journal for clinicians.

[67]  T. Hibi,et al.  MicroRNAs in Gastric Cancer , 2011 .

[68]  Jian Liang,et al.  The mechanism involved in the loss of PTEN expression in NSCLC tumor cells. , 2012, Biochemical and biophysical research communications.

[69]  R. Aharonov,et al.  hsa-miR-29c* is linked to the prognosis of malignant pleural mesothelioma. , 2010, Cancer research.

[70]  H. Ezelle,et al.  Regulation of human RNase-L by the miR-29 family reveals a novel oncogenic role in chronic myelogenous leukemia. , 2013, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[71]  Xing-zhen Sun,et al.  Prognostic value of miR-29a expression in pediatric acute myeloid leukemia. , 2013, Clinical biochemistry.

[72]  Jin-Wu Nam,et al.  miR-29 miRNAs activate p53 by targeting p85α and CDC42 , 2009, Nature Structural &Molecular Biology.

[73]  George A Calin,et al.  MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. , 2008, Blood.

[74]  R. Kalluri,et al.  miR-29b moulds the tumour microenvironment to repress metastasis , 2013, Nature Cell Biology.

[75]  H. Mollenkopf,et al.  Reference miRNAs for miRNAome Analysis of Urothelial Carcinomas , 2012, PloS one.

[76]  G. Gores,et al.  mir-29 regulates Mcl-1 protein expression and apoptosis , 2007, Oncogene.

[77]  B. Jacobsen,et al.  Progestin regulated miRNAs that mediate progesterone receptor action in breast cancer , 2012, Molecular and Cellular Endocrinology.

[78]  Yilin Yang,et al.  A microRNA expression signature predicts meningioma recurrence , 2013, International journal of cancer.

[79]  Xianwei Wang,et al.  The regulatory roles of miRNA and methylation on oncogene and tumor suppressor gene expression in pancreatic cancer cells. , 2012, Biochemical and biophysical research communications.

[80]  M. Loda,et al.  miR-29b Expression Is Associated With Disease-Free Survival in Patients With Ovarian Serous Carcinoma , 2009, International Journal of Gynecologic Cancer.

[81]  T. Pabst,et al.  The tumour-suppressive miR-29a/b1 cluster is regulated by CEBPA and blocked in human AML , 2010, British Journal of Cancer.

[82]  Tint Lwin,et al.  microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. , 2010, Blood.

[83]  L. Cantley,et al.  Oncogenes and signal transduction , 1991, Cell.

[84]  Longgui Wang,et al.  Serum microRNA-29a is a promising novel marker for early detection of colorectal liver metastasis. , 2012, Cancer epidemiology.

[85]  Wei Zhang,et al.  miR‐29b and miR‐125a regulate podoplanin and suppress invasion in glioblastoma , 2010, Genes, chromosomes & cancer.

[86]  Tsung-Cheng Chang,et al.  Widespread microRNA repression by Myc contributes to tumorigenesis , 2008, Nature Genetics.

[87]  G. Goodall,et al.  Matrigel basement membrane matrix influences expression of microRNAs in cancer cell lines. , 2012, Biochemical and biophysical research communications.