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Non-coding RNAs in Endocrinology

Ed. by Hardikar, Anandwardhan

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MicroRNAs and pancreatic-endocrine system

Ettore Luzi
  • Regional Center on Endocrine Hereditary Tumors, AOUC, and Bone Metabolic Unit Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Federica D’Asta
  • 2Department of Neurosciences, Psychology, Drug Area and Child Health, University of Florence, Florence, Italy
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  • De Gruyter OnlineGoogle Scholar
/ Maria Luisa Brandi
  • Corresponding author
  • Regional Center on Endocrine Hereditary Tumors, AOUC, and Bone Metabolic Unit Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2014-07-26 | DOI: https://doi.org/10.2478/micrnado-2013-0003


MicroRNAs (miRNAs) are endogenous single-stranded non-coding RNAs of about - 22 nucleotides which suppress gene expression by selectively binding to the 3’ non coding region (3’-UTR) of specific messenger RNAs through base-pairing. There are now more than 1600 human miRNAs annotated in the miRNA registry (http://microrna.sanger.ac.uk), but, at the moment, very few miRNAs have been well characterized and most of their roles remain unknown. miRNAs derive from transcripts that fold back on themselves to form distinctive hairpin structures, whereas the other types of endogenous small RNAs derive either from much longer hairpins that give rise to a greater diversity of small RNAs (siRNAs), or from bimolecular RNA duplexes (siRNAs), or from precursors without any suspected doublestranded character (piRNAs). The key step to understanding more about the possible functions of microRNA is to identify their mRNA targets.

Recent studies have supported a role of miRNAs in the initiation and progression of human malignancies. Several groups have studied the global miRNA expression in cancer patients and found that miRNAs show different patterns of expression in normal and tumor tissues. The involvement of miRNAs in human cancer is probably due to the fact that >50% of miRNA genes are located at chromosomal regions, such as fragile sites or common break point sites, and regions of deletion or amplification that are generally altered in human tumors. Experimental evidence has shown that miRNA expression profiles enable the classification of poorly characterized human tumors that cannot be accurately classified using only the mRNA expression patterns. As a result, the miRs involved in the oncogenic transformation process are being investigated as novel biomarkers of disease detection and prognosis as well as potential therapeutic targets for human cancers. The aim of this review is to provide a general background regarding current knowledge about miRNA involvement in human pancreatic cancer and in the regulation of glucose metabolism.

Keywords: MicroRNAs; Tumorigenesis; Pancreatic cancer; Glucose metabolism


  • [1] Lee I, Ajay SS, Yook JI, Kim HS, Hong SH, Kim NH, Dhanasekaran SM, Chinnaiyan AM, Athey BD. “New class of microRNA targets containing simultaneous 5’-UTR and 3’- UTR interaction sites” Genome Res 19: 1175-1183, 2009.CrossrefGoogle Scholar

  • [2] Lewis BP, Burge CB, Bartel DP. “Conserved seed pairing, often flanked by adenosines , indicates that thousands of human genes are microRNA targets” Cell 120: 15-20, 2005.Google Scholar

  • [3] Griffiths-Jones S. “The microRNA Registry”. Nucleic Acids Res 32 (Database issue):D109-111, 2004.CrossrefGoogle Scholar

  • [4] Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E. “Phylogenetic shadowing and computational identification of human microRNA genes”. Cell 120 (1): 21-24, 2005.Google Scholar

  • [5] Brown JR, Sanseau P.“A computational view of microRNAs and their targets.” Drug Discovery Today 10: 595-601, 2005.CrossrefPubMedGoogle Scholar

  • [6] Calin GA, Croce CM. “MicroRNA-cancer connection: the beginning of a new tale”. Cancer Res 66 (15): 7390-7394, 2006.Google Scholar

  • [7] Michael MZ, O’ Connor SM, van Holst Pellekaan NG, Young GP, James RJ. “Reduced accumulation of specific microRNAs in colorectal neoplasia”. Mol Cancer Res 1 (12): 882-891, 2003.Google Scholar

  • [8] Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M, Dell’Aquila ML, Alder H, Rassenti L, Kipps TJ, Bullrich F, Negrini M, Croce CM. “MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias”. Proc Natl Acad Sci U S A 101 (32): 11755-11760, 2004.CrossrefGoogle Scholar

  • [9] Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. “A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukaemia”. N Engl J Med 353 (17): 1793-1801, 2005.Google Scholar

  • [10] Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF, Lund E, Dahlberg JE. “Accumulation of miR-155 and BIC RNA in human B cell lymphomas”. Proc Natl Acad Sci U S A 102 (10): 3627-3632, 2005.CrossrefGoogle Scholar

  • [11] Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T. “Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival”. Cancer Res 64 (11): 3753-3756, 2004.CrossrefGoogle Scholar

  • [12] Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Menard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM. “MicroRNA gene expression deregulation in human breast cancer”. Cancer Res 65 (16): 7065-7070, 2005.CrossrefGoogle Scholar

  • [13] Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG. “Extensive modulation of a set of microRNAs in primary glioblastoma”. Biochem Biophys Res Commun. 334 (4): 1351-1358, 2005.Google Scholar

  • [14] Chan JA, Krichevsky AM, Kosik KS. “MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells”. Cancer Res 65 (14): 6029-6033, 2005.CrossrefGoogle Scholar

  • [15] Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM. “Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers”. Proc Natl Acad Sci U S A 101 (9): 2999-3004, 2004.CrossrefGoogle Scholar

  • [16] Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. “MicroRNA expression profiles classify human cancers”. Nature 435 (7043): 834-838, 2005.Google Scholar

  • [17] Lau NC, Lim LP, Weinstein EG, Bartel DP. ”An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans” Science 294 (5543):858-862, 2001. Google Scholar

  • [18] Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. “Identification of novel genes coding for small expressed RNAs”. Science 294 (5543):853-858, 2001.Google Scholar

  • [19] Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G. “miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs”. Genes Dev. 16 (6): 720-728, 2002.CrossrefGoogle Scholar

  • [20] Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, Kim VN. “The nuclear RNase III Drosha initiates microRNA processing”. Nature 425 (6956): 415-419, 2003.Google Scholar

  • [21] Yi R, Qin Y, Macara IG, Cullen BR. “Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs”. Genes Dev 17 (24): 3011-3016, 2003.CrossrefGoogle Scholar

  • [22] Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD. “A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA”. Science 293 (5531): 834-838, 2001.Google Scholar

  • [23] Tang G. “siRNA and miRNA: an insight into RISCs”. Trends Biochem Sci 30: 106-114, 2005.CrossrefGoogle Scholar

  • [24] Hutvagner G, Zamore PD. “A microRNA in a multiple-turnover RNAi enzyme complex”. Science 297 (5589): 2056-2060, 2002.Google Scholar

  • [25] Zeng Y, Cullen BR. “Sequence requirements for micro RNA processing and function in human cells”. RNA (9): 112-133, 2003.CrossrefGoogle Scholar

  • [26] Llave C, Xie Z, Kasschau KD, Carrington JC. “Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA”. Science 297 (5589): 2053-2056, 2002.Google Scholar

  • [27] Yekta S, Shih IH, Bartel DP. “MicroRNA-directed cleavage of HOXB8 mRNA”. Science 304 (5670): 594-596, 2004.Google Scholar

  • [28] Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P, Stoffel M. “A pancreatic islet-specific microRNA regulates insulin secretion”. Nature 432 (7014): 226-230, 2004.Google Scholar

  • [29] Poy MN, Hausser J, Trajkovski M, Braun M, Collins S, Rorsman P, Zavolan M, Stoffel M.”miR-375 maintains normal pancreatic alpha- and beta-cell mass”. Proc Natl Acad Sci U S A.106(14):5813-8, 2009 .Google Scholar

  • [30] Avnit-Sagi T, Kantorovich L, Kredo-Russo S, Hornstein E, Walker MD.”The promoter of the pri-miR-375 gene directs expression selectively to the endocrine pancreas”. PLoS One. 4(4):e5033. Epub 2009.Google Scholar

  • [31] Joglekar MV, Joglekar VM, Hardikar AA. “Expression of isletspecific microRNAs during human pancreatic development” Gene Expr Patterns. 9(2):109-13, 2009.Google Scholar

  • [32] Li Y, Xu X, Liang Y, Liu S, Xiao H, Li F, Cheng H, Fu Z. “miR-375 enhances palmitate-induced lipoapoptosis in insulinsecreting NIT-1 cells by repressing myotrophin (V1) protein expression”. Int J Clin Exp Pathol. 3(3): 254-64, 2010.Google Scholar

  • [33] Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N. “Combinatorial microRNA target predictions.”. Nat Genet 37 : 495-500, 2005. CrossrefGoogle Scholar

  • [34] Plaisance V, Abderrahmani A, Perret-Menoud V, Jacquemin P, Lemaigre F, Regazzi R. “MicroRNA-9 controls the expression of Granuphilin/Slp4 and the secretory response of insulinproducing cells”. J Biol Chem 281: 26932-26942, 2006.Google Scholar

  • [35] Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S, Calin GA, Volinia S, Liu CG, Scarpa A, Croce CM. “MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior”. J Clin Oncol 24: 4677-4684, 2006.CrossrefGoogle Scholar

  • [36] Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL, Morgan DL, Postier RG, Brackett DJ, Schmittgen TD.”Expression profiling identifies microRNA signature in pancreatic cancer”. Int J Cancer. 120(5):1046-54, 2007.Google Scholar

  • [37] Bolmeson C, Esguerra JL, Salehi A, Speidel D, Eliasson L, Cilio CM. “Differences in islet-enriched miRNAs in healthy and glucose intolerant human subjects”. Biochem Biophys Res Commun. 404(1):16-22. Epub 2010 Nov 19.Google Scholar

  • [38] X. Chen, Y. Ba, L. Ma “Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases “ Cell Res 18 , pp. 997-1006, 2008.CrossrefGoogle Scholar

  • [39] P.S. Mitchell, R.K. Parkin, E.M. Kroh, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O’Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M.”Circulating microRNAs as stable blood-based markers for cancer detection” Proc Natl Acad Sci U S A 105 :10513-1051, 2008.Google Scholar

  • [40] Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, Benjamin H, Kushnir M, Cholakh H, Melamed N, Bentwich Z, Hod M, Goren Y, Chajut A.Serum microRNAs are promising novel biomarkers PLoS One, 3 , p. e3148, 2008.Google Scholar

  • [41] N. Scholer, C. Langer, H. Dohner, C. Buske, F. Kuchenbauer Serum microRNAs as a novel class of biomarkers: a comprehensive review of the literature Exp Hematol, 38: 1126-1130, 2010.CrossrefGoogle Scholar

  • [42] S. Mathivanan, H. Ji, R.J. Simpson “Exosomes: extracellular organelles important in intercellular communication” J Proteomics, 73: 1907-1920,2010.CrossrefGoogle Scholar

  • [43] G. Camussi, M.C. Deregibus, S. Bruno, V. Cantaluppi, L. Biancone “Exosomes/microvesicles as a mechanism of cellto- cell communication” Kidney Int, 78: 838-84,2010. CrossrefGoogle Scholar

  • [44] Guay C, Roggli E, Nesca V, Jacovetti C, Regazzi R. “Diabetes mellitus, a microRNA-related disease? “Transl Res. 157(4): 253-64, 2011.Google Scholar

  • [45] Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M. “Silencing of microRNAs in vivo with ‘antagomirs’. “Nature. 438(7068):685-9. Epub 2005 Oct 30,2005.Google Scholar

  • [46] Kato, M., Arce, L., Wang, M., Putta, S., Lanting, L., & Natarajan, R. “A microRNA circuit mediates transforming growth factor-beta1 autoregulation in renal glomerular mesangial cells”. Kidney International, 80: 358-368, 2011.Google Scholar

  • [47] Kato, M., Putta, S., Wang, M., Yuan, H., Lanting, L., Nair, I., “TGF-beta activates Akt kinase through a microRNAdependent amplifying circuit targeting PTEN.” Nature Cell Biology, 11: 881-889, 2009.CrossrefGoogle Scholar

  • [48] Putta, S., Lanting, L., Sun, G., Lawson, G., Kato, M., & Natarajan, R. “Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy.” Journal of the American Society of Nephrology, 23: 458-469,2012.Google Scholar

  • [49] Ebert MS, Sharp PA.”MicroRNA sponges: progress and possibilities”. RNA 16(11):2043-50, 2010.CrossrefGoogle Scholar

  • [50] Kluiver J, Gibcus JH, Hettinga C, Adema A, Richter MK, Halsema N, Slezak-Prochazka I, Ding Y, Kroesen BJ, van den Berg A.”Rapid generation of microRNA sponges for microRNA inhibition”. PLoS One. 7(1):e29275. Epub 2012 Jan 6.Google Scholar

  • [51] Andrali SS, Sampley ML, Vanderford NL, Ozcan S. “Glucose regulation of insulin gene expression in pancreatic betacells”. Biochem J 415: 1-10, 2008.Google Scholar

  • [52] Cerf ME .”Transcription factors regulating beta-cell function.” Eur J Endocrinol 155: 671-679, 2008.Google Scholar

  • [53] Martinez NJ, Walhout AJ. “The interplay between transcription factors and microRNAs in genome-scale regulatory networks”.Bioessays. 31(4):435-445. 2009. doi: 10.1002/bies.200800212.CrossrefGoogle Scholar

  • [54] Melkman-Zehavi T, Oren R, Kredo-Russo S, Shapira T, Mandelbaum AD, Rivkin N, Nir T, Lennox KA, Behlke MA, Dor Y, Hornstein E.”miRNAs control insulin content in pancreatic β-cells via downregulation of transcriptional repressors”. EMBO 30(5):835-45. 2011. Epub 2011 Feb 1.CrossrefGoogle Scholar

  • [55] Lynn FC, Skewes-Cox P, Kosaka Y, McManus MT, Harfe BD, German MS .” MicroRNA expression is required for pancreatic islet cell genesis in the mouse.” Diabetes 56: 2938-2945,2007. CrossrefGoogle Scholar

About the article

Received: 2012-12-10

Revised: 2013-02-28

Accepted: 2013-03-05

Published Online: 2014-07-26

Published in Print: 2014-07-01

Citation Information: Non-coding RNAs in Endocrinology, Volume 1, Issue 1, ISSN (Online) 2300-4258, DOI: https://doi.org/10.2478/micrnado-2013-0003.

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