Skip to main content

Insights into the Role of microRNAs in Pancreatic Cancer Pathogenesis: Potential for Diagnosis, Prognosis, and Therapy

  • Chapter
microRNA: Cancer

Abstract

Pancreatic cancer is a highly lethal malignancy and a fourth leading cause of cancer-related death in the United States. Poor survival of pancreatic cancer patients is largely because of its asymptomatic progression to advanced stage against which no effective therapy is currently available. Over the years, we have developed significant knowledge of molecular progression of pancreatic cancer and identified several genetic and epigenetic aberrations to be involved in its etiology and aggressive behavior. In that regard, recent lines of evidence have suggested important roles of microRNAs (miRNAs/miRs) in pancreatic cancer pathogenesis. microRNAs belonging to a family of small, noncoding RNAs are able to control diverse biological processes due to their ability to regulate gene expression at the posttranscriptional level. Accordingly, dysregulation of miRNAs can lead to several disease conditions, including cancer. There is a long list of microRNAs that exhibit aberrant expression in pancreatic cancer and serve as key microplayers in its initiation, progression, metastasis, and chemoresistance. These findings have suggested that microRNAs could be exploited as novel biomarkers for diagnostic and prognostic assessments of pancreatic cancer and as targets for therapy. This book chapter describes clinical problems associated with pancreatic cancer, roles that microRNAs play in various aspects of pancreatic cancer pathogenesis, and envision opportunities for potential use of microRNAs in pancreatic cancer management.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Iorio MV, Croce CM. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med. 2012;4:143–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Jansson MD, Lund AH. MicroRNA and cancer. Mol Oncol. 2012;6:590–610.

    Article  CAS  PubMed  Google Scholar 

  3. Friedlander MR, Lizano E, Houben AJ, et al. Evidence for the biogenesis of more than 1,000 novel human microRNAs. Genome Biol. 2014;15:R57.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Jin Y, Chen Z, Liu X, Zhou X. Evaluating the microRNA targeting sites by luciferase reporter gene assay. Methods Mol Biol. 2013;936:117–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Saetrom P, Heale BS, Snove Jr O, Aagaard L, Alluin J, Rossi JJ. Distance constraints between microRNA target sites dictate efficacy and cooperativity. Nucleic Acids Res. 2007;35:2333–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Srivastava SK, Arora S, Singh S, Bhardwaj A, Averett C, Singh AP. MicroRNAs in pancreatic malignancy: progress and promises. Cancer Lett. 2014;347:167–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bhardwaj A, Singh S, Singh AP. MicroRNA-based cancer therapeutics: big hope from small RNAs. Mol Cell Pharmacol. 2010;2:213–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Von Hoff DD, Korn R, Mousses S. Pancreatic cancer--could it be that simple? A different context of vulnerability. Cancer Cell. 2009;16:7–8.

    Article  Google Scholar 

  9. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–21.

    Article  CAS  PubMed  Google Scholar 

  10. Ozdemir BC, Pentcheva-Hoang T, Carstens JL, et al. Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell. 2014;25:719–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tyagi N, Bhardwaj A, Singh AP, McClellan S, Carter JE, Singh S. p-21 activated kinase 4 promotes proliferation and survival of pancreatic cancer cells through AKT- and ERK-dependent activation of NF-kappaB pathway. Oncotarget. 2014;5:8778–89.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Rachagani S, Macha MA, Heimann N, et al. Clinical implications of miRNAs in the pathogenesis, diagnosis and therapy of pancreatic cancer. Adv Drug Deliv Rev. 2015;81:16–33.

    Article  CAS  PubMed  Google Scholar 

  13. Omura N, Goggins M. Epigenetics and epigenetic alterations in pancreatic cancer. Int J Clin Exp Pathol. 2009;2:310–26.

    CAS  PubMed  Google Scholar 

  14. Arora S, Bhardwaj A, Singh S, et al. An undesired effect of chemotherapy: gemcitabine promotes pancreatic cancer cell invasiveness through reactive oxygen species-dependent, nuclear factor kappaB- and hypoxia-inducible factor 1alpha-mediated up-regulation of CXCR4. J Biol Chem. 2013;288:21197–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hruban RH, Takaori K, Canto M, et al. Clinical importance of precursor lesions in the pancreas. J Hepatobiliary Pancreat Surg. 2007;14:255–63.

    Article  PubMed  Google Scholar 

  16. Hruban RH, Fukushima N. Pancreatic adenocarcinoma: update on the surgical pathology of carcinomas of ductal origin and PanINs. Mod Pathol. 2007;20 Suppl 1:S61–70.

    Article  PubMed  Google Scholar 

  17. Kaur S, Baine MJ, Jain M, Sasson AR, Batra SK. Early diagnosis of pancreatic cancer: challenges and new developments. Biomark Med. 2012;6:597–612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Nentwich MF, Konig A, Izbicki JR. Limits of surgery for pancreatic cancer. Rozhl Chir. 2014;93:445–9.

    CAS  PubMed  Google Scholar 

  19. Olive KP, Jacobetz MA, Davidson CJ, et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 2009;324:1457–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25:1960–6.

    Article  CAS  PubMed  Google Scholar 

  21. Colucci G, Labianca R, Di CF, et al. Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol. 2010;28:1645–51.

    Article  CAS  PubMed  Google Scholar 

  22. Conroy T, Gavoille C, Samalin E, Ychou M, Ducreux M. The role of the FOLFIRINOX regimen for advanced pancreatic cancer. Curr Oncol Rep. 2013;15:182–9.

    Article  CAS  PubMed  Google Scholar 

  23. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703.

    Article  Google Scholar 

  24. Poy MN, Eliasson L, Krutzfeldt J, et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 2004;432:226–30.

    Article  CAS  PubMed  Google Scholar 

  25. Lee EJ, Gusev Y, Jiang J, et al. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer. 2007;120:1046–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhang Y, Li M, Wang H, et al. Profiling of 95 microRNAs in pancreatic cancer cell lines and surgical specimens by real-time PCR analysis. World J Surg. 2009;33:698–709.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Srivastava SK, Bhardwaj A, Singh S, et al. MicroRNA-150 directly targets MUC4 and suppresses growth and malignant behavior of pancreatic cancer cells. Carcinogenesis. 2011;32:1832–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ali S, Ahmad A, Banerjee S, et al. Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF. Cancer Res. 2010;70:3606–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bloomston M, Frankel WL, Petrocca F, et al. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA. 2007;297:1901–8.

    Article  CAS  PubMed  Google Scholar 

  30. Olson P, Lu J, Zhang H, et al. MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer. Genes Dev. 2009;23:2152–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ohuchida K, Mizumoto K, Lin C, et al. MicroRNA-10a is overexpressed in human pancreatic cancer and involved in its invasiveness partially via suppression of the HOXA1 gene. Ann Surg Oncol. 2012;19:2394–402.

    Article  PubMed  Google Scholar 

  32. Ryu JK, Hong SM, Karikari CA, Hruban RH, Goggins MG, Maitra A. Aberrant MicroRNA-155 expression is an early event in the multistep progression of pancreatic adenocarcinoma. Pancreatology. 2010;10:66–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. He H, Di Y, Liang M, et al. The microRNA-218 and ROBO-1 signaling axis correlates with the lymphatic metastasis of pancreatic cancer. Oncol Rep. 2013;30:651–8.

    CAS  PubMed  Google Scholar 

  34. Yu J, Li A, Hong SM, Hruban RH, Goggins M. MicroRNA alterations of pancreatic intraepithelial neoplasias. Clin Cancer Res. 2012;18:981–92.

    Article  PubMed  Google Scholar 

  35. Morimura R, Komatsu S, Ichikawa D, et al. Novel diagnostic value of circulating miR-18a in plasma of patients with pancreatic cancer. Br J Cancer. 2011;105:1733–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ali S, Saleh H, Sethi S, Sarkar FH, Philip PA. MicroRNA profiling of diagnostic needle aspirates from patients with pancreatic cancer. Br J Cancer. 2012;107:1354–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Chang TC, Wentzel EA, Kent OA, et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007;26:745–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ji Q, Hao X, Zhang M, et al. MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS One. 2009;4, e6816.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Yu S, Lu Z, Liu C, et al. miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. Cancer Res. 2010;70:6015–25.

    Article  CAS  PubMed  Google Scholar 

  40. Kent OA, Chivukula RR, Mullendore M, et al. Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway. Genes Dev. 2010;24:2754–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Khan S, Ebeling MC, Zaman MS, et al. MicroRNA-145 targets MUC13 and suppresses growth and invasion of pancreatic cancer. Oncotarget. 2014;5:7599–609.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Keklikoglou I, Hosaka K, Bender C, et al. MicroRNA-206 functions as a pleiotropic modulator of cell proliferation, invasion and lymphangiogenesis in pancreatic adenocarcinoma by targeting ANXA2 and KRAS genes. Oncogene. 2014. doi:10.1038/onc.2014.408.

  43. Guo R, Gu J, Zhang Z, Wang Y, Gu C. MicroRNA-410 functions as a tumor suppressor by targeting angiotensin II type 1 receptor in pancreatic cancer. IUBMB Life. 2015;67(1):42–53. doi:10.1002/iub.1342.

    Article  CAS  PubMed  Google Scholar 

  44. Bao B, Ali S, Ahmad A, et al. Hypoxia-induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment. PLoS One. 2012;7, e50165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Zhao WG, Yu SN, Lu ZH, Ma YH, Gu YM, Chen J. The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS. Carcinogenesis. 2010;31:1726–33.

    Article  CAS  PubMed  Google Scholar 

  46. Lu Z, Li Y, Takwi A, et al. miR-301a as an NF-kappaB activator in pancreatic cancer cells. EMBO J. 2011;30:57–67.

    Article  CAS  PubMed  Google Scholar 

  47. Liu L, Nie J, Chen L, et al. The oncogenic role of microRNA-130a/301a/454 in human colorectal cancer via targeting Smad4 expression. PLoS One. 2013;8, e55532.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Torrisani J, Bournet B, du Rieu MC, et al. let-7 MicroRNA transfer in pancreatic cancer-derived cells inhibits in vitro cell proliferation but fails to alter tumor progression. Hum Gene Ther. 2009;20:831–44.

    Article  CAS  PubMed  Google Scholar 

  49. Tsuda N, Ishiyama S, Li Y, Ioannides CG, Abbruzzese JL, Chang DZ. Synthetic microRNA designed to target glioma-associated antigen 1 transcription factor inhibits division and induces late apoptosis in pancreatic tumor cells. Clin Cancer Res. 2006;12:6557–64.

    Article  CAS  PubMed  Google Scholar 

  50. Lee KH, Lotterman C, Karikari C, et al. Epigenetic silencing of MicroRNA miR-107 regulates cyclin-dependent kinase 6 expression in pancreatic cancer. Pancreatology. 2009;9:293–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Zhang R, Li M, Zang W, et al. MiR-148a regulates the growth and apoptosis in pancreatic cancer by targeting CCKBR and Bcl-2. Tumour Biol. 2014;35:837–44.

    Article  CAS  PubMed  Google Scholar 

  52. Kawaguchi T, Komatsu S, Ichikawa D, et al. Clinical impact of circulating miR-221 in plasma of patients with pancreatic cancer. Br J Cancer. 2013;108:361–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Sarkar S, Dubaybo H, Ali S, et al. Down-regulation of miR-221 inhibits proliferation of pancreatic cancer cells through up-regulation of PTEN, p27(kip1), p57(kip2), and PUMA. Am J Cancer Res. 2013;3:465–77.

    PubMed  PubMed Central  Google Scholar 

  54. Wu K, Hu G, He X, et al. MicroRNA-424-5p suppresses the expression of SOCS6 in pancreatic cancer. Pathol Oncol Res. 2013;19:739–48.

    Article  CAS  PubMed  Google Scholar 

  55. Xu D, Wang Q, An Y, Xu L. MiR203 regulates the proliferation, apoptosis and cell cycle progression of pancreatic cancer cells by targeting Survivin. Mol Med Rep. 2013;8:379–84.

    PubMed  Google Scholar 

  56. Huang C, Li H, Wu W, Jiang T, Qiu Z. Regulation of miR-155 affects pancreatic cancer cell invasiveness and migration by modulating the STAT3 signaling pathway through SOCS1. Oncol Rep. 2013;30:1223–30.

    CAS  PubMed  Google Scholar 

  57. Mees ST, Mardin WA, Wendel C, et al. EP300—a miRNA-regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas. Int J Cancer. 2010;126:114–24.

    Article  CAS  PubMed  Google Scholar 

  58. Weiss FU, Marques IJ, Woltering JM, et al. Retinoic acid receptor antagonists inhibit miR-10a expression and block metastatic behavior of pancreatic cancer. Gastroenterology. 2009;137:2136–45.

    Article  CAS  PubMed  Google Scholar 

  59. Ouyang H, Gore J, Deitz S, Korc M. microRNA-10b enhances pancreatic cancer cell invasion by suppressing TIP30 expression and promoting EGF and TGF-beta actions. Oncogene. 2014;33:4664–74.

    Article  CAS  PubMed  Google Scholar 

  60. Nakata K, Ohuchida K, Mizumoto K, et al. MicroRNA-10b is overexpressed in pancreatic cancer, promotes its invasiveness, and correlates with a poor prognosis. Surgery. 2011;150:916–22.

    Article  PubMed  Google Scholar 

  61. Giovannetti E, Funel N, Peters GJ, et al. MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. Cancer Res. 2010;70:4528–38.

    Article  CAS  PubMed  Google Scholar 

  62. Roldo C, Missiaglia E, Hagan JP, et al. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol. 2006;24:4677–84.

    Article  CAS  PubMed  Google Scholar 

  63. Kadera BE, Li L, Toste PA, et al. MicroRNA-21 in pancreatic ductal adenocarcinoma tumor-associated fibroblasts promotes metastasis. PLoS One. 2013;8, e71978.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Li Y, Vandenboom TG, Wang Z, et al. miR-146a suppresses invasion of pancreatic cancer cells. Cancer Res. 2010;70:1486–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Hu Y, Ou Y, Wu K, Chen Y, Sun W. miR-143 inhibits the metastasis of pancreatic cancer and an associated signaling pathway. Tumour Biol. 2012;33:1863–70.

    Article  CAS  PubMed  Google Scholar 

  66. Frampton AE, Krell J, Jacob J, Stebbing J, Castellano L, Jiao LR. Loss of miR-126 is crucial to pancreatic cancer progression. Expert Rev Anticancer Ther. 2012;12:881–4.

    Article  CAS  PubMed  Google Scholar 

  67. Hamada S, Satoh K, Fujibuchi W, et al. MiR-126 acts as a tumor suppressor in pancreatic cancer cells via the regulation of ADAM9. Mol Cancer Res. 2012;10:3–10.

    Article  CAS  PubMed  Google Scholar 

  68. Liu C, Cheng H, Shi S, et al. MicroRNA-34b inhibits pancreatic cancer metastasis through repressing Smad3. Curr Mol Med. 2013;13:467–78.

    Article  CAS  PubMed  Google Scholar 

  69. Bhutia YD, Hung SW, Krentz M, et al. Differential processing of let-7a precursors influences RRM2 expression and chemosensitivity in pancreatic cancer: role of LIN-28 and SET oncoprotein. PLoS One. 2013;8, e53436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Maftouh M, Avan A, Funel N, et al. miR-211 modulates gemcitabine activity through downregulation of ribonucleotide reductase and inhibits the invasive behavior of pancreatic cancer cells. Nucleosides Nucleotides Nucleic Acids. 2014;33:384–93.

    Article  CAS  PubMed  Google Scholar 

  71. Hasegawa S, Eguchi H, Nagano H, et al. MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer. Br J Cancer. 2014;111:1572–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Singh S, Chitkara D, Kumar V, Behrman SW, Mahato RI. miRNA profiling in pancreatic cancer and restoration of chemosensitivity. Cancer Lett. 2013;334:211–20.

    Article  CAS  PubMed  Google Scholar 

  73. Yan HJ, Liu WS, Sun WH, et al. miR-17-5p inhibitor enhances chemosensitivity to gemcitabine via upregulating Bim expression in pancreatic cancer cells. Dig Dis Sci. 2012;57:3160–7.

    Article  CAS  PubMed  Google Scholar 

  74. Dong J, Zhao YP, Zhou L, Zhang TP, Chen G. Bcl-2 upregulation induced by miR-21 via a direct interaction is associated with apoptosis and chemoresistance in MIA PaCa-2 pancreatic cancer cells. Arch Med Res. 2011;42:8–14.

    Article  CAS  PubMed  Google Scholar 

  75. Bera A, VenkataSubbaRao K, Manoharan MS, Hill P, Freeman JW. A miRNA signature of chemoresistant mesenchymal phenotype identifies novel molecular targets associated with advanced pancreatic cancer. PLoS One. 2014;9, e106343.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Chen Z, Sangwan V, Banerjee S, et al. miR-204 mediated loss of Myeloid cell leukemia-1 results in pancreatic cancer cell death. Mol Cancer. 2013;12:105–12.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Iwagami Y, Eguchi H, Nagano H, et al. miR-320c regulates gemcitabine-resistance in pancreatic cancer via SMARCC1. Br J Cancer. 2013;109:502–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Dillhoff M, Liu J, Frankel W, Croce C, Bloomston M. MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. J Gastrointest Surg. 2008;12:2171–6.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Szafranska AE, Davison TS, John J, et al. MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene. 2007;26:4442–52.

    Article  CAS  PubMed  Google Scholar 

  80. Szafranska AE, Doleshal M, Edmunds HS, et al. Analysis of microRNAs in pancreatic fine-needle aspirates can classify benign and malignant tissues. Clin Chem. 2008;54:1716–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kong X, Du Y, Wang G, et al. Detection of differentially expressed microRNAs in serum of pancreatic ductal adenocarcinoma patients: miR-196a could be a potential marker for poor prognosis. Dig Dis Sci. 2011;56:602–9.

    Article  CAS  PubMed  Google Scholar 

  82. Li A, Yu J, Kim H, et al. MicroRNA array analysis finds elevated serum miR-1290 accurately distinguishes patients with low-stage pancreatic cancer from healthy and disease controls. Clin Cancer Res. 2013;19:3600–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Goggins M. Identifying molecular markers for the early detection of pancreatic neoplasia. Semin Oncol. 2007;34:303–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Gold DV, Modrak DE, Ying Z, Cardillo TM, Sharkey RM, Goldenberg DM. New MUC1 serum immunoassay differentiates pancreatic cancer from pancreatitis. J Clin Oncol. 2006;24:252–8.

    Article  CAS  PubMed  Google Scholar 

  85. Habbe N, Koorstra JB, Mendell JT, et al. MicroRNA miR-155 is a biomarker of early pancreatic neoplasia. Cancer Biol Ther. 2009;8:340–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Hwang JH, Voortman J, Giovannetti E, et al. Identification of microRNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer. PLoS One. 2010;5, e10630.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Ohuchida K, Mizumoto K, Kayashima T, et al. MicroRNA expression as a predictive marker for gemcitabine response after surgical resection of pancreatic cancer. Ann Surg Oncol. 2011;18:2381–7.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Zhang Y, Yang J, Cui X, et al. A novel epigenetic CREB-miR-373 axis mediates ZIP4-induced pancreatic cancer growth. EMBO Mol Med. 2013;5:1322–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Ikenaga N, Ohuchida K, Mizumoto K, et al. MicroRNA-203 expression as a new prognostic marker of pancreatic adenocarcinoma. Ann Surg Oncol. 2010;17:3120–8.

    Article  PubMed  Google Scholar 

  90. Pramanik D, Campbell NR, Karikari C, et al. Restitution of tumor suppressor microRNAs using a systemic nanovector inhibits pancreatic cancer growth in mice. Mol Cancer Ther. 2011;10:1470–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Park JK, Lee EJ, Esau C, Schmittgen TD. Antisense inhibition of microRNA-21 or -221 arrests cell cycle, induces apoptosis, and sensitizes the effects of gemcitabine in pancreatic adenocarcinoma. Pancreas. 2009;38:e190–9.

    Article  CAS  PubMed  Google Scholar 

  92. Park JK, Henry JC, Jiang J, et al. miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor. Biochem Biophys Res Commun. 2011;406:518–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Yan H, Wu J, Liu W, et al. MicroRNA-20a overexpression inhibited proliferation and metastasis of pancreatic carcinoma cells. Hum Gene Ther. 2010;21:1723–34.

    Article  CAS  PubMed  Google Scholar 

  94. Wang P, Zhang J, Zhang L, et al. MicroRNA 23b regulates autophagy associated with radioresistance of pancreatic cancer cells. Gastroenterology. 2013;145:1133–43.

    Article  CAS  PubMed  Google Scholar 

  95. Zhao G, Wang B, Liu Y, et al. miRNA-141, downregulated in pancreatic cancer, inhibits cell proliferation and invasion by directly targeting MAP4K4. Mol Cancer Ther. 2013;12:2569–80.

    Article  CAS  PubMed  Google Scholar 

  96. Zhao Y, Zhao L, Ischenko I, et al. Antisense inhibition of microRNA-21 and microRNA-221 in tumor-initiating stem-like cells modulates tumorigenesis, metastasis, and chemotherapy resistance in pancreatic cancer. Target Oncol. 2015. doi 10.1007/s11523-015-0360-2.

Download references

Acknowledgements

Grant support: NIH/NCI [CA137513, CA167137, CA175772, CA185490 (to APS) and CA169829 (to SS)], DOD/US Army [PC110545 and PC0739930 (to APS)] and USAMCI. Conflicts of Interest: No potential conflict of interest to disclose.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ajay Pratap Singh Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Khan, M.A., Zubair, H., Srivastava, S.K., Singh, S., Singh, A.P. (2015). Insights into the Role of microRNAs in Pancreatic Cancer Pathogenesis: Potential for Diagnosis, Prognosis, and Therapy. In: Santulli, G. (eds) microRNA: Cancer. Advances in Experimental Medicine and Biology, vol 889. Springer, Cham. https://doi.org/10.1007/978-3-319-23730-5_5

Download citation

Publish with us

Policies and ethics