Hostname: page-component-586b7cd67f-dlnhk Total loading time: 0 Render date: 2024-11-25T18:00:37.178Z Has data issue: false hasContentIssue false

Impact of miRNAs in gastrointestinal cancer diagnosis and prognosis

Published online by Cambridge University Press:  14 October 2010

Bo Song
Affiliation:
Translational Research Laboratory, Department of Pathology, State University of New York at Stony Brook, Stony Brook, NY, USA.
Jingfang Ju*
Affiliation:
Translational Research Laboratory, Department of Pathology, State University of New York at Stony Brook, Stony Brook, NY, USA.
*
*Corresponding author: Jingfang Ju, Translational Research Laboratory, BST L9, Room 185, Department of Pathology, Stony Brook University Medical Center, Stony Brook, NY 11794-8691, USA. E-mail: [email protected]

Abstract

Since the discovery of noncoding small RNAs such as microRNAs (miRNAs), and their roles as potential tumour suppressors or oncogenes, post-transcriptional and translational control of gene expression have become increasingly important in cancer research. Given that over a third of coding genes, as estimated by computational prediction, are regulated by miRNAs, various types of cancer will show direct association with changes in miRNA expression. The link of certain miRNAs with specific developmental stages, tissues and cancer contributes to their strong potential as biomarkers and novel therapeutic targets. In this review, we cover recent advances in miRNA research in human gastrointestinal cancer (colorectal, gastric, pancreatic and liver) and the potential of miRNAs as diagnostic and prognostic biomarkers.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Fire, A. et al. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806-811CrossRefGoogle ScholarPubMed
2Lee, R.C., Feinbaum, R.L. and Ambros, V. (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854CrossRefGoogle Scholar
3Wightman, B., Ha, I. and Ruvkun, G. (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75, 855-862CrossRefGoogle ScholarPubMed
4Calin, G.A. et al. (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America 99, 15524-15529CrossRefGoogle ScholarPubMed
5Bartel, D.P. (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297Google Scholar
6Cummins, J.M. et al. (2006) The colorectal microRNAome. Proceedings of the National Academy of Sciences of the United States of America 103, 3687-3692Google Scholar
7Esquela-Kerscher, A. and Slack, F.J. (2006) Oncomirs - microRNAs with a role in cancer. Nature Reviews. Cancer 6, 259-269CrossRefGoogle ScholarPubMed
8Pillai, R.S. et al. (2005) Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science 309, 1573-1576CrossRefGoogle ScholarPubMed
9Ruvkun, G. (2006) Clarifications on miRNA and cancer. Science 311, 36-37Google Scholar
10Dony, C., Kessel, M. and Gruss, P. (1985) Post-transcriptional control of myc and p53 expression during differentiation of the embryonal carcinoma cell line F9. Nature 317, 636-639CrossRefGoogle ScholarPubMed
11Jemal, A. et al. (2009) Cancer statistics, 2009. CA: A Cancer Journal for Clinicians 59, 225-249Google ScholarPubMed
12Weisenberger, D.J. et al. (2006) CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nature Genetics 38, 787-793Google Scholar
13Widschwendter, M. et al. (2007) Epigenetic stem cell signature in cancer. Nature Genetics 39, 157-158CrossRefGoogle ScholarPubMed
14Calin, G.A. and Croce, C.M. (2006) MicroRNA-cancer connection: the beginning of a new tale. Cancer Research 66, 7390-7394Google Scholar
15Bartels, C.L. and Tsongalis, G.J. (2009) MicroRNAs: novel biomarkers for human cancer. Clinical Chemistry 55, 623-631CrossRefGoogle ScholarPubMed
16Bandrés, E. et al. (2006) Identification by real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Molecular Cancer 5, 29CrossRefGoogle ScholarPubMed
17Schetter, A.J. et al. (2008) MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. Journal of the American Medical Association 299, 425-436Google Scholar
18Slaby, O. et al. (2007) Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology 72, 397-402Google Scholar
19Volinia, S. et al. (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proceedings of the National Academy of Sciences of the United States of America 103, 2257-2261CrossRefGoogle ScholarPubMed
20Michael, M.Z. et al. (2003) Reduced accumulation of specific microRNAs in colorectal neoplasia. Molecular Cancer Research 1, 882-891Google ScholarPubMed
21Chen, X. et al. (2009) Role of miR-143 targeting KRAS in colorectal tumorigenesis. Oncogene 28, 1385-1392Google Scholar
22Akao, Y., Nakagawa, Y. and Naoe, T. (2006) MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncology Reports 16, 845-850Google Scholar
23Ng, E.K. et al. (2009) MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer. British Journal of Cancer 101, 699-706Google Scholar
24English, J.M. et al. (1998) Identification of substrates and regulators of the mitogen-activated protein kinase ERK5 using chimeric protein kinases. Journal of Biological Chemistry 273, 3854-3860CrossRefGoogle ScholarPubMed
25Borralho, P.M. et al. (2009) MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in HCT116 human colorectal cancer cells. FEBS Journal 276, 6689-6700CrossRefGoogle ScholarPubMed
26Shi, B. et al. (2007) Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. Journal of Biological Chemistry 282, 32582-32590Google Scholar
27La Rocca, G. et al. (2009) Mechanism of growth inhibition by MicroRNA 145: the role of the IGF-I receptor signaling pathway. Journal of Cellular Physiology 220, 485-491CrossRefGoogle ScholarPubMed
28Guo, C. et al. (2008) The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers. Genes, Chromosomes and Cancer 47, 939-946CrossRefGoogle ScholarPubMed
29Grady, W.M. et al. (2008) Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer. Oncogene 27, 3880-3888Google Scholar
30Strillacci, A. et al. (2009) MiR-101 downregulation is involved in cyclooxygenase-2 overexpression in human colon cancer cells. Experimental Cell Research 315, 1439-1447Google Scholar
31Xi, Y. et al. (2006) Differentially regulated micro-RNAs and actively translated messenger RNA transcripts by tumor suppressor p53 in colon cancer. Clinical Cancer Research 12, 2014-2024Google Scholar
32He, L. et al. (2007) A microRNA component of the p53 tumour suppressor network. Nature 447, 1130-1134Google Scholar
33Chang, T.C. et al. (2007) Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Molecular Cell 26, 745-752CrossRefGoogle ScholarPubMed
34Raver-Shapira, N. et al. (2007) Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Molecular Cell 26, 731-743Google Scholar
35Tazawa, H. et al. (2007) Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proceedings of the National Academy of Sciences of the United States of America 104, 15472-15477Google Scholar
36Yamakuchi, M., Ferlito, M. and Lowenstein, C.J. (2008) miR-34a repression of SIRT1 regulates apoptosis. Proceedings of the National Academy of Sciences of the United States of America 105, 13421-13426CrossRefGoogle ScholarPubMed
37Ji, J. et al. (2009) MicroRNA expression, survival, and response to interferon in liver cancer. New England Journal of Medicine 361, 1437-1447Google Scholar
38Kota, J. et al. (2009) Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137, 1005-1017CrossRefGoogle Scholar
39Song, B. et al. (2008) miR-192 Regulates dihydrofolate reductase and cellular proliferation through the p53-microRNA circuit. Clinical Cancer Research 14, 8080-8086Google Scholar
40Sara, A. et al. (2008) Coordinated regulation of cell cycle transcripts by p53-inducible microRNAs, miR-192 and miR-215. Cancer Research 68, 10105-10112Google Scholar
41Christian, J. et al. (2008) p53-responsive microRNAs 192 and 215 are capable of inducing cell cycle arrest. Cancer Research 68, 10094-10104Google Scholar
42Ju, J., Song, B. and Wang, Y. (2009) Impacts of microRNA-215 on cell proliferation and chemotherapy resistance in colon cancer and osteosarcoma. Journal of Clinical Oncology (2009 ASCO Annual Meeting Proceedings) 27, 2542Google Scholar
43Song, B., Wang, Y., Titmus, M.A., Botchkina, G., Formentini, A., Kornmann, M., Ju, J. (2010) Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cells. Mol Cancer 9, 96CrossRefGoogle ScholarPubMed
44Mishra, P.J. et al. (2009) MiR-24 tumor suppressor activity is regulated independent of p53 and through a target site polymorphism. PLoS One 4, e8445CrossRefGoogle ScholarPubMed
45Lal, A. et al. (2009) miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to “seedless” 3′UTR microRNA recognition elements. Molecular Cell 35, 610-625CrossRefGoogle Scholar
46Yamamichi, N. et al. (2009) Locked nucleic acid in situ hybridization analysis of miR-21 expression during colorectal cancer development. Clinical Cancer Research 15, 4009-4016Google Scholar
47Frankel, L.B. et al. (2008) Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. Journal of Biological Chemistry 283, 1026-1033CrossRefGoogle ScholarPubMed
48Asangani, I.A. et al. (2008) MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27, 2128-2136Google Scholar
49Mendell, J.T. (2008) miRiad roles for the miR-17–92 cluster in development and disease. Cell 133, 217-222Google Scholar
50Diosdado, B. et al. (2009) MiR-17–92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression. British Journal of Cancer 101, 707-714Google Scholar
51Monzo, M. et al. (2008) Overlapping expression of microRNAs in human embryonic colon and colorectal cancer. Cell Research 18, 823-833CrossRefGoogle ScholarPubMed
52O'Donnell, K.A. et al. (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435, 839-843Google Scholar
53Woods, K., Thomson, J.M. and Hammond, S.M. (2007) Direct regulation of an oncogenic micro-RNA cluster by E2F transcription factors. Journal of Biological Chemistry 282, 2130-2134Google Scholar
54Diaz, R. et al. (2008) Deregulated expression of miR-106a predicts survival in human colon cancer patients. Genes, Chromosomes and Cancer 47, 794-802CrossRefGoogle ScholarPubMed
55Xi, Y. et al. (2006) Prognostic values of microRNAs in colorectal cancer. Biomark Insights 2, 113-121Google Scholar
56Nakajima, G. et al. (2006) Non-coding microRNAs hsa-let-7g and hsa-miR-181b are associated with chemoresponse to S-1 in colon cancer. Cancer Genomics and Proteomics 3, 317-324Google Scholar
57Chim, S.S. et al. (2008) Detection and characterization of placental microRNAs in maternal plasma. Clinical Chemistry 54, 482-490CrossRefGoogle ScholarPubMed
58Lawrie, C.H. et al. (2008) Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. British Journal of Haematology 141, 672-675Google Scholar
59Wong, T.S. et al. (2008) Mature miR-184 as potential oncogenic microRNA of squamous cell carcinoma of tongue. Clinical Cancer Research 14, 2588-2592Google Scholar
60Mitchell, P.S. et al. (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proceedings of the National Academy of Sciences of the United States of America 105, 10513-10518Google Scholar
61Ng, E.K. et al. (2009) Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 58, 1375-1381CrossRefGoogle ScholarPubMed
62Huang, Z. et al. (2010) Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. International Journal of Cancer 127, 118-126Google Scholar
63Schetter, A.J. and Harris, C.C. (2009) Plasma microRNAs: a potential biomarker for colorectal cancer? Gut 58, 1318-1319Google Scholar
64Forman, D. and Burley, V.J. (2006) Gastric cancer: global pattern of the disease and an overview of environmental risk factors. Best Practice and Research. Clinical Gastroenterology 20, 633-649Google Scholar
65Liu, T. et al. (2009) MicroRNA-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitin. Cancer Letters 273, 233-242CrossRefGoogle ScholarPubMed
66Guo, J. et al. (2009) Differential expression of microRNA species in human gastric cancer versus non-tumorous tissues. Journal of Gastroenterology and Hepatology 24, 652-657Google Scholar
67Luo, H. et al. (2009) Down-regulated miR-9 and miR-433 in human gastric carcinoma. Journal of Experimental and Clinical Cancer Research 28, 82Google Scholar
68Ueda, T. et al. (2010) Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncology 11, 136-146Google Scholar
69Bandrés, E. et al. (2009) microRNA-451 regulates macrophage migration inhibitory factor production and proliferation of gastrointestinal cancer cells. Clinical Cancer Research 15, 2281-2290CrossRefGoogle ScholarPubMed
70Gregory, P.A. et al. (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biology 10, 593-601CrossRefGoogle ScholarPubMed
71Korpal, M. et al. (2008) The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. Journal of Biological Chemistry 283, 14910-14914Google Scholar
72Du, Y. et al. (2009) Down-regulation of miR-141 in gastric cancer and its involvement in cell growth. Journal of Gastroenterology 44, 556-561Google Scholar
73Takagi, T. et al. (2009) Decreased expression of microRNA-143 and -145 in human gastric cancers. Oncology 77, 12-21CrossRefGoogle ScholarPubMed
74Zhang, Y. et al. (2010) Down-regulation of miR-31 expression in gastric cancer tissues and its clinical significance. Medical Oncology 27, 685-689Google Scholar
75Wan, H.Y. et al. Regulation of the transcription factor NF-kappaB1 by microRNA-9 in human gastric adenocarcinoma. Molecular Cancer 9, 16Google Scholar
76Petrocca, F. et al. (2008) E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 13, 272-286Google Scholar
77Xiao, B. et al. (2009) Detection of miR-106a in gastric carcinoma and its clinical significance. Clinica Chimica Acta 400, 97-102Google Scholar
78Kim, Y.K. et al. (2009) Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer. Nucleic Acids Research 37, 1672-1681Google Scholar
79Zhang, Z. et al. (2008) miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Laboratory Investment 88, 1358-1366Google Scholar
80Jiang, Z. et al. Increased expression of miR-421 in human gastric carcinoma and its clinical association. Journal of Gastroenterology 45, 17-23Google Scholar
81Wu, Q. et al. MiR-150 promotes gastric cancer proliferation by negatively regulating the pro-apoptotic gene EGR2. Biochemical and Biophysical Research Communications 392, 340-345Google Scholar
82Xia, L. et al. (2008) miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. International Journal of Cancer 123, 372-379Google Scholar
83Murakami, Y. et al. (2006) Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 25, 2537-2545CrossRefGoogle ScholarPubMed
84Huang, Y.S. et al. (2008) Microarray analysis of microRNA expression in hepatocellular carcinoma and non-tumorous tissues without viral hepatitis. Journal of Gastroenterology and Hepatology 23, 87-94Google Scholar
85Wang, Y. et al. (2008) Profiling microRNA expression in hepatocellular carcinoma reveals microRNA-224 up-regulation and apoptosis inhibitor-5 as a microRNA-224-specific target. Journal of Biological Chemistry 283, 13205-13215Google Scholar
86Ladeiro, Y. et al. (2008) MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. Hepatology 47, 1955-1963Google Scholar
87Huang, X.H. et al. (2009) Bead-based microarray analysis of microRNA expression in hepatocellular carcinoma: miR-338 is downregulated. Hepatology Research 39, 786-794Google Scholar
88Su, H. et al. (2009) MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Research 69, 1135-1142Google Scholar
89Gramantieri, L. et al. (2007) Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Research 67, 6092-6099Google Scholar
90Jiang, J. et al. (2008) Association of MicroRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival. Clinical Cancer Research 14, 419-427Google Scholar
91Ura, S. et al. (2009) Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma. Hepatology 49, 1098-1112Google Scholar
92Wong, Q.W. et al. (2008) MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1. Gastroenterology 135, 257-269Google Scholar
93Chang, J. et al. (2004) miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biology 1, 106-113Google Scholar
94Lagos-Quintana, M. et al. (2001) Identification of novel genes coding for small expressed RNAs. Science 294(5543), 853-858CrossRefGoogle ScholarPubMed
95Esau, C. et al. (2006) miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metabolism 3, 87-98Google Scholar
96Meng, F. et al. (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133, 647-658Google Scholar
97Kutay, H. et al. (2006) Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. Journal of Cellular Biochemistry 99, 671-678CrossRefGoogle ScholarPubMed
98Coulouarn, C. et al. (2009) Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene 28, 3526-3536Google Scholar
99Bai, S. et al. (2009) MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. Journal of Biological Chemistry 284, 32015-32027Google Scholar
100Lin, C.J. et al. (2008) miR-122 targets an anti-apoptotic gene, Bcl-w, in human hepatocellular carcinoma cell lines. Biochemical and Biophysical Research Communications 375, 315-320CrossRefGoogle ScholarPubMed
101Llovet, J.M. et al. (2008) Sorafenib in advanced hepatocellular carcinoma. New England Journal of Medicine 359, 378-390CrossRefGoogle ScholarPubMed
102Fornari, F. et al. (2009) MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Research 69, 5761-5767Google Scholar
103Li, N. et al. (2009) miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Letters 275, 44-53Google Scholar
104Li, S. et al. (2009) MicroRNA-101 regulates expression of the v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene in human hepatocellular carcinoma. Hepatology 49, 1194-1202Google Scholar
105Salvi, A. et al. (2009) MicroRNA-23b mediates urokinase and c-met downmodulation and a decreased migration of human hepatocellular carcinoma cells. FEBS Journal 276, 2966-2982Google Scholar
106Wong, Q.W. et al. MiR-222 overexpression confers cell migratory advantages in hepatocellular carcinoma through enhancing AKT signaling. Clinical Cancer Research 16, 867-875Google Scholar
107Xu, T. et al. (2009) MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells. Hepatology 50, 113-121Google Scholar
108Connolly, E. et al. (2008) Elevated expression of the miR-17–92 polycistron and miR-21 in hepadnavirus-associated hepatocellular carcinoma contributes to the malignant phenotype. American Journal of Pathology 173, 856-864Google Scholar
109Fornari, F. et al. (2008) MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene 27, 5651-5661Google Scholar
110Gramantieri, L. et al. (2009) MicroRNA-221 targets Bmf in hepatocellular carcinoma and correlates with tumor multifocality. Clinical Cancer Research 15, 5073-5081Google Scholar
111Pineau, P. et al. miR-221 overexpression contributes to liver tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America 107, 264-269CrossRefGoogle Scholar
112Garofalo, M. et al. (2009) miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell 16, 498-509Google Scholar
113Wang, B. et al. (2009) Role of microRNA-155 at early stages of hepatocarcinogenesis induced by choline-deficient and amino acid-defined diet in C57BL/6 mice. Hepatology 50, 1152-1161Google Scholar
114Li, Y. et al. (2009) Role of the miR-106b-25 microRNA cluster in hepatocellular carcinoma. Cancer Science 100, 1234-1242Google Scholar
115Yamamoto, Y. et al. (2009) MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma. Biomarkers 14, 529-538CrossRefGoogle ScholarPubMed
116Li, W. et al. (2008) Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma. International Journal of Cancer 123, 1616-1622Google Scholar
117Budhu, A. et al. (2008) Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology 47, 897-907Google Scholar
118Bloomston, M. et al. (2007) MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. Journal of American Medical Association 297, 1901-1908Google Scholar
119Greither, T. et al. Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. International Journal of Cancer 126, 73-80Google Scholar
120Garcea, G. et al. (2005) Molecular prognostic markers in pancreatic cancer: a systematic review. European Journal of Cancer 41, 2213-2236Google Scholar
121Lu, J. et al. (2005) MicroRNA expression profiles classify human cancers. Nature 435, 834-838Google Scholar
122Lee, E.J. et al. (2007) Expression profiling identifies microRNA signature in pancreatic cancer. International Journal of Cancer 120, 1046-1054Google Scholar
123Szafranska, A.E. et al. (2007) MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene 26, 4442-4452Google Scholar
124Zhang, Y. et al. (2009) Profiling of 95 microRNAs in pancreatic cancer cell lines and surgical specimens by real-time PCR analysis. World Journal of Surgery 33, 698-709Google Scholar
125Seux, M. et al. (2009) MicroRNAs in pancreatic ductal adenocarcinoma: new diagnostic and therapeutic clues. Pancreatology 9, 66-72Google Scholar
126Poy, M.N. et al. (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432, 226-230Google Scholar
127Szafranska, A.E. et al. (2008) Analysis of microRNAs in pancreatic fine-needle aspirates can classify benign and malignant tissues. Clinical Chemistry 54, 1716-1724Google Scholar
128Torrisani, J. et al. (2009) let-7 MicroRNA transfer in pancreatic cancer-derived cells inhibits in vitro cell proliferation but fails to alter tumor progression. Human Gene Therapy 20, 831-844Google Scholar
129Dillhoff, M. et al. (2008) MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. Journal of Gastrointestinal Surgery 12, 2171-2176Google Scholar
130Gao, C. et al. (2010) Reduced microRNA-218 expression is associated with high nuclear factor kappa B activation in gastric cancer. Cancer 116, 41-49Google Scholar

Further reading, resources and contacts

Lee, R.C., Feinbaum, R.L. and Ambros, V. (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854Google Scholar
Fire, A. et al. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806-811Google Scholar
Calin, G.A. et al. (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America 99, 15524-15529Google Scholar
Bartel, D.P. (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297Google Scholar
Xi, Y. et al. (2006) Differentially regulated micro-RNAs and actively translated messenger RNA transcripts by tumor suppressor p53 in colon cancer. Clinical Cancer Research 12, 2014-2024Google Scholar