MiR-377 reverses cancerous phenotypes of pancreatic cells via suppressing DNMT1 and demethylating tumor suppressor genes

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References

• 1 Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J. Clin. 63(1), 11–30 (2013).
  MedlineGoogle Scholar
• 2 Li J, Wientjes MG, Au JL. Pancreatic cancer: pathobiology, treatment options, and drug delivery. AAPS J. 12(2), 223–232 (2010).
  Medline CASGoogle Scholar
• 3 Werner J, Combs SE, Springfeld C, Hartwig W, Hackert T, Buchler MW. Advanced-stage pancreatic cancer: therapy options. Nat. Rev. Clin. Oncol. 10(6), 323–333 (2013).
  Medline CASGoogle Scholar
• 4 Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N. Engl. J. Med. 371(11), 1039–1049 (2014).
  Medline CASGoogle Scholar
• 5 Delpu Y, Hanoun N, Lulka H et al. Genetic and epigenetic alterations in pancreatic carcinogenesis. Curr. Genomics 12(1), 15–24 (2011).
  Medline CASGoogle Scholar
• 6 Arai E, Kanai Y. DNA methylation profiles in precancerous tissue and cancers: carcinogenetic risk estimation and prognostication based on DNA methylation status. Epigenomics 2(3), 467–481 (2010).
  CASGoogle Scholar
• 7 Jair KW, Bachman KE, Suzuki H et al. De novo CpG island methylation in human cancer cells. Cancer Res. 66(2), 682–692 (2006).
  Medline CASGoogle Scholar
• 8 Denis H, Ndlovu MN, Fuks F. Regulation of mammalian DNA methyltransferases: a route to new mechanisms. EMBO Rep. 12(7), 647–656 (2011). • A review about the regulatory mechanisms involved in the dynamic interplay between interdependent post-translational modifications that regulate DNMTs, post-transcriptional regulation by miRNAs and the emerging role of noncoding RNA in targeting mammalian DNMTs.
  Medline CASGoogle Scholar
• 9 Ting AH, Jair KW, Schuebel KE, Baylin SB. Differential requirement for DNA methyltransferase 1 in maintaining human cancer cell gene promoter hypermethylation. Cancer Res. 66(2), 729–735 (2006).
  Medline CASGoogle Scholar
• 10 Li A, Omura N, Hong SM, Goggins M. Pancreatic cancer DNMT1 expression and sensitivity to DNMT1 inhibitors. Cancer Biol. Ther. 9(4), 321–329 (2010).
  Medline CASGoogle Scholar
• 11 Goyal R, Rathert P, Laser H, Gowher H, Jeltsch A. Phosphorylation of serine-515 activates the mammalian maintenance methyltransferase Dnmt1. Epigenetics 2(3), 155–160 (2007).
  MedlineGoogle Scholar
• 12 Kanai Y, Hirohashi S. Alterations of DNA methylation associated with abnormalities of DNA methyltransferases in human cancers during transition from a precancerous to a malignant state. Carcinogenesis 28(12), 2434–2442 (2007).
  Medline CASGoogle Scholar
• 13 Etoh T, Kanai Y, Ushijima S et al. Increased DNA methyltransferase 1 (DNMT1) protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers. Am. J. Pathol. 164(2), 689–699 (2004).
  Medline CASGoogle Scholar
• 14 Saito Y, Kanai Y, Nakagawa T et al. Increased protein expression of DNA methyltransferase (DNMT) 1 is significantly correlated with the malignant potential and poor prognosis of human hepatocellular carcinomas. Int. J. Cancer 105(4), 527–532 (2003).
  Medline CASGoogle Scholar
• 15 Peng DF, Kanai Y, Sawada M et al. Increased DNA methyltransferase 1 (DNMT1) protein expression in precancerous conditions and ductal carcinomas of the pancreas. Cancer Sci. 96(7), 403–408 (2005).
  Medline CASGoogle Scholar
• 16 Sun M, Hurst LD, Carmichael GG, Chen J. Evidence for a preferential targeting of 3′-UTRs by cis-encoded natural antisense transcripts. Nucleic Acids Res. 33(17), 5533–5543 (2005).
  Medline CASGoogle Scholar
• 17 Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2), 281–297 (2004).
  Medline CASGoogle Scholar
• 18 Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19(1), 92–105 (2009).
  Medline CASGoogle Scholar
• 19 Suzuki H, Maruyama R, Yamamoto E, Kai M. DNA methylation and microRNA dysregulation in cancer. Mol. Oncol. 6(6), 567–578 (2012). • Describes the role of DNA methylation in microRNA dysregulation in cancer and explains that the aberrant DNA methylation of miRNA genes is a potentially useful biomarker for detecting cancer and predicting its outcome.
  Medline CASGoogle Scholar
• 20 Rachagani S, Kumar S, Batra SK. MicroRNA in pancreatic cancer: pathological, diagnostic and therapeutic implications. Cancer Lett. 292(1), 8–16 (2010). • Describes the differential expression pattern of miRNAs in pancreatic tumors and their use for diagnostic and therapeutic purposes.
  Medline CASGoogle Scholar
• 21 Vasilatou D, Papageorgiou SG, Dimitriadis G, Pappa V. Epigenetic alterations and microRNAs: new players in the pathogenesis of myelodysplastic syndromes. Epigenetics 8(6), 561–570 (2013).
  Medline CASGoogle Scholar
• 22 Hildebrandt MA, Gu J, Lin J et al. Hsa-miR-9 methylation status is associated with cancer development and metastatic recurrence in patients with clear cell renal cell carcinoma. Oncogene 29(42), 5724–5728 (2010).
  Medline CASGoogle Scholar
• 23 Kozaki K, Imoto I, Mogi S, Omura K, Inazawa J. Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Res. 68(7), 2094–2105 (2008).
  Medline CASGoogle Scholar
• 24 Hanoun N, Delpu Y, Suriawinata AA et al. The silencing of microRNA 148a production by DNA hypermethylation is an early event in pancreatic carcinogenesis. Clin. Chem. 56(7), 1107–1118 (2010). • Hypermethylation and inactivation of miRNAs in pancreatic ductal adenocarcinoma (PDAC) is an early event during pancreatic carcinogenesis and these differentially methylated regions can serve as a diagnostic marker for PDAC.
  Medline CASGoogle Scholar
• 25 Stumpel DJ, Schotte D, Lange-Turenhout EA et al. Hypermethylation of specific microRNA genes in MLL-rearranged infant acute lymphoblastic leukemia: major matters at a micro scale. Leukemia 25(3), 429–439 (2011).
  Medline CASGoogle Scholar
• 26 Kita Y, Vincent K, Natsugoe S, Berindan-Neagoe I, Calin GA. Epigenetically regulated microRNAs and their prospect in cancer diagnosis. Expert Rev. Mol. Diagn. 14(6), 673–683 (2014).
  Medline CASGoogle Scholar
• 27 Lomberk GA, Iovanna J, Urrutia R. The promise of epigenomic therapeutics in pancreatic cancer. Epigenomics 8(6), 831–842 (2016).
  CASGoogle Scholar
• 28 Braconi C, Huang N, Patel T. MicroRNA-dependent regulation of DNA methyltransferase-1 and tumor suppressor gene expression by interleukin-6 in human malignant cholangiocytes. Hepatology 51(3), 881–890 (2010).
  Medline CASGoogle Scholar
• 29 Azizi M, Teimori-Toolabi L, Arzanani MK et al. MicrRNA-148b and microRNA-152 reactivate tumor suppressor genes through suppressin of DNA methyltransferase-1 gene in panvreatic cancer cell line. Cancer Biol. Ther. 14(5), 419–427 (2014).
  Google Scholar
• 30 Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 30(9), e36 (2002).
  MedlineGoogle Scholar
• 31 Chen C, Ridzon DA, Broomer AJ et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 33(20), e179 (2005).
  MedlineGoogle Scholar
• 32 Mohammadi-Yeganeh S, Paryan M, MirabSamiee S et al. Development of a robust, low cost stem-loop real-time quantification PCR technique for miRNA expression analysis. Mol. Biol. Rep. 40(5), 3665–3674 (2013).
  Medline CASGoogle Scholar
• 33 The mfold Web Server. http://mfold.rna.albany.edu/?q=mfold/.
  Google Scholar
• 34 DataBase of CpG islands and Analytical Tools (DBCAT). http://dbcat.cgm.ntu.edu.tw/.
  Google Scholar
• 35 John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human microRNA targets. PLoS Biol. 2(11), e363 (2004).
  MedlineGoogle Scholar
• 36 Lewis BP, Shih I-H, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell 115(7), 787–798 (2003).
  Medline CASGoogle Scholar
• 37 Krek A, Grün D, Poy MN et al. Combinatorial microRNA target predictions. Nat. Genetics 37(5), 495–500 (2005).
  Medline CASGoogle Scholar
• 38 Omura N, Goggins M. Epigenetics and epigenetic alterations in pancreatic cancer. Int. J. Clin. Exp. Pathol. 2(4), 310–326 (2009).
  Medline CASGoogle Scholar
• 39 Mizuno S, Chijiwa T, Okamura T et al. Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia. Blood 97(5), 1172–1179 (2001).
  Medline CASGoogle Scholar
• 40 Nguyen T, Kuo C, Nicholl MB et al. Downregulation of microRNA-29c is associated with hypermethylation of tumor-related genes and disease outcome in cutaneous melanoma. Epigenetics 6(3), 388–394 (2011).
  Medline CASGoogle Scholar
• 41 Huang J, Wang Y, Guo Y, Sun S. Down-regulated microRNA-152 induces aberrant DNA methylation in hepatitis B virus-related hepatocellular carcinoma by targeting DNA methyltransferase 1. Hepatology 52(1), 60–70 (2010).
  Medline CASGoogle Scholar
• 42 Formosa A, Markert EK, Lena AM et al. MicroRNAs, miR-154, miR-299–5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485–3p, miR-495 and miR-654–3p, mapped to the 14q32.31 locus, regulate proliferation, apoptosis, migration and invasion in metastatic prostate cancer cells. Oncogene 33(44), 5173–5182 (2013).
  MedlineGoogle Scholar
• 43 Zhang L, Volinia S, Bonome T et al. Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc. Natl Acad. Sci. USA 105(19), 7004–7009 (2008).
  Medline CASGoogle Scholar
• 44 Wong KY, Yu L, Chim CS. DNA methylation of tumor suppressor miRNA genes: a lesson from the miR-34 family. Epigenomics 3(1), 83–92 (2011). • Describes the role of miRNA methylation, in particular miR-34a, the gene structure of the miR-34 family of miRNA genes, the tumor suppressor role of miR-34a and the deregulation of miR-34a by DNA methylation in both epithelial and hematological cancers.
  CASGoogle Scholar
• 45 Zhang S, Hao J, Xie F et al. Downregulation of miR-132 by promoter methylation contributes to pancreatic cancer development. Carcinogenesis 32(8), 1183–1189 (2011).
  Medline CASGoogle Scholar
• 46 Guo X, Xia J, Yan J. Promoter methylated microRNAs: potential therapeutic targets in gastric cancer (Review). Mol. Med. Rep. 11(2), 759–765 (2015).
  Medline CASGoogle Scholar
• 47 Manuyakorn A, Paulus R, Farrell J et al. Cellular histone modification patterns predict prognosis and treatment response in resectable pancreatic adenocarcinoma: results from RTOG 9704. J. Clin. Oncol. 28(8), 1358–1365 (2010).
  Medline CASGoogle Scholar
• 48 Zhang W, Dahlberg JE, Tam W. MicroRNAs in tumorigenesis: a primer. Am. J. Pathol. 171(3), 728–738 (2007).
  Medline CASGoogle Scholar
• 49 Venturelli S, Berger A, Weiland T et al. Differential induction of apoptosis and senescence by the DNA methyltransferase inhibitors 5-azacytidine and 5-aza-2′-deoxycytidine in solid tumor cells. Mol. Cancer Ther. 12(10), 2226–2236 (2013). • Describing antiproliferative activity, cytotoxicity, gene demethylation, transcription, natural killer(NK) cell activity, or DNA repair effects of the 2 closely related DNMTi nucleoside analogues 5-aza-CR and 5-aza-dC in solid tumor cells.
  Medline CASGoogle Scholar
• 50 Azad MB, Gibson SB. Role of BNIP3 in proliferation and hypoxia-induced autophagy: implications for personalized cancer therapies. Ann. New York Acad. Sci. 1210, 8–16 (2010).
  Medline CASGoogle Scholar
• 51 Okami J, Simeone DM, Logsdon CD. Silencing of the hypoxia-inducible cell death protein BNIP3 in pancreatic cancer. Cancer Res. 64(15), 5338–5346 (2004).
  Medline CASGoogle Scholar
• 52 Abe T, Toyota M, Suzuki H et al. Upregulation of BNIP3 by 5-aza-2′-deoxycytidine sensitizes pancreatic cancer cells to hypoxia-mediated cell death. J. Gastroenterol. 40(5), 504–510 (2005).
  Medline CASGoogle Scholar
• 53 Sato N, Fukushima N, Maehara N et al. SPARC/osteonectin is a frequent target for aberrant methylation in pancreatic adenocarcinoma and a mediator of tumor-stromal interactions. Oncogene 22(32), 5021–5030 (2003).
  Medline CASGoogle Scholar
• 54 Puolakkainen PA, Brekken RA, Muneer S, Sage EH. Enhanced growth of pancreatic tumors in SPARC-null mice is associated with decreased deposition of extracellular matrix and reduced tumor cell apoptosis. Mol. Cancer Res. 2(4), 215–224 (2004).
  Medline CASGoogle Scholar
• 55 Mahadevan D, Von Hoff DD. Tumor–stroma interactions in pancreatic ductal adenocarcinoma. Mol. Cancer Ther. 6(4), 1186–1197 (2007).
  Medline CASGoogle Scholar