New Association Between Diabetes Mellitus and Pancreatic Cancer

Monireh      Rezaei; Zinat      Shams; Bahareh   Sadat   Rasouli; Katayoun   Dadeh   Amirfard; Mohadeseh   Soleymani   Sadrabadi; Ali      Gheysarzadeh; Karimeh      Haghani; Salar      Bakhtiyari
Abstract

Background: Diabetes mellitus is a global issue that has affected the lives of many people all over the world. This disorder, which is also called the mother of all diseases, possesses high pathogenicity and results in the emergence of many disorders. One of the known correlated diseases is pancreatic cancer which can be accompanied by diabetes mellitus. Therefore, finding the association between these diseases and common genes is urgent.
Objective: In this study, in order to survey the relationship between diabetes mellitus and pancreatic cancer, the common genes of these disorders were analyzed by bioinformatics tools.
Methods: For this purpose, we screened 17 shared genes from microarray data downloaded from the Gene Expression Omnibus (GEO) database. In addition, the relationship between identified genes was constructed by STRING and DAVID tools.
Results: In total, 112 genes were identified to be differentially expressed. Among these, 17 genes were found to be common, including two genes that were down-regulated and others that were upregulated. Other analyses showed that most of the genes were enriched in Vibrio cholera infection and the mTOR signaling pathway. The biological processes of such genes included oxygen and gas transport, phagosome acidification, and GTPase activity.
Conclusion: In this study, 17 common genes that had not previously been considered in diabetes and pancreatic cancer were screened, which can be further considered for clinical approaches and in vitro studies.
Keywords: Diabetes, pancreatic cancer, bioinformatics, gene expression omnibus, string, DAVID tools.
[1]
Carracher AM, Marathe PH, Close KL. International diabetes federation 2017. J Diabetes  2018; 10(5): 353-6.
 [http://dx.doi.org/10.1111/1753-0407.12644] [PMID: 29345068]

[2]
Bell ET. Carcinoma of the pancreas. I. A clinical and pathologic study of 609 necropsied cases. II. The relation of carcinoma of the pancreas to diabetes mellitus. Am J Pathol  1957; 33(3): 499-523.
 [PMID: 13424657]

[3]
Noto H, Tsujimoto T, Sasazuki T, Noda M. Significantly increased risk of cancer in patients with diabetes mellitus: A systematic review and meta-analysis. Endocr Pract  2011; 17(4): 616-28.
 [http://dx.doi.org/10.4158/EP10357.RA] [PMID: 21454235]

[4]
Huang Y, Cai X, Qiu M, et al. Prediabetes and the risk of cancer: A meta-analysis.  Diabetologia  2014; 57(11): 2261-9.

[5]
Cignarelli A, Genchi VA, Caruso I, et al. Diabetes and cancer: Pathophysiological fundamentals of a ‘dangerous affair’. Diabetes Res Clin Pract  2018; 143: 378-88.
 [http://dx.doi.org/10.1016/j.diabres.2018.04.002] [PMID: 29679627]

[6]
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(11): 2913-21.
 [http://dx.doi.org/10.1158/0008-5472.CAN-14-0155] [PMID: 24840647]

[7]
Kinjyo I, Hanada T, Inagaki-Ohara K, et al. SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. Immunity  2002; 17(5): 583-91.
 [http://dx.doi.org/10.1016/S1074-7613(02)00446-6] [PMID: 12433365]

[8]
Gheysarzadeh A, Bakhtiari H, Ansari A, Emami Razavi A, Emami MH. The insulin-like growth factor binding protein‐3 and its death receptor in pancreatic ductal adenocarcinoma poor prognosis. Mofid MRJJocp  2019; 234(12): 23537-46.

[9]
O’Carroll D, Schaefer A. General principals of miRNA biogenesis and regulation in the brain. Neuropsychopharmacology  2013; 38(1): 39-54.
 [http://dx.doi.org/10.1038/npp.2012.87] [PMID: 22669168]

[10]
Wang L, Tsutsumi S, Kawaguchi T, et al. Whole-exome sequencing of human pancreatic cancers and characterization of genomic instability caused by MLH1 haploinsufficiency and complete deficiency. Genome Res  2012; 22(2): 208-19.
 [http://dx.doi.org/10.1101/gr.123109.111] [PMID: 22156295]

[11]
Waddell N, Pajic M, Patch A-M, et al. Australian Pancreatic Cancer Genome Initiative. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature  2015; 518(7540): 495-501.
 [http://dx.doi.org/10.1038/nature14169] [PMID: 25719666]

[12]
Swords DS, Firpo MA, Scaife CL, Mulvihill SJ. Biomarkers in pancreatic adenocarcinoma: Current perspectives. OncoTargets Ther  2016; 9: 7459-67.
 [http://dx.doi.org/10.2147/OTT.S100510] [PMID: 28003762]

[13]
Gumbs AA. Obesity, pancreatitis, and pancreatic cancer. Obes Surg  2008; 18(9): 1183-7.
 [http://dx.doi.org/10.1007/s11695-008-9599-3] [PMID: 18563497]

[14]
Li D, Abbruzzese JL. New strategies in pancreatic cancer: Emerging epidemiologic and therapeutic concepts. Clin Cancer Res  2010; 16(17): 4313-8.
 [http://dx.doi.org/10.1158/1078-0432.CCR-09-1942] [PMID: 20647474]

[15]
Decensi A, Puntoni M, Goodwin P, et al. Metformin and cancer risk in diabetic patients: A systematic review and meta-analysis. Cancer Prev Res (Phila)  2010; 3(11): 1451-61.
 [http://dx.doi.org/10.1158/1940-6207.CAPR-10-0157] [PMID: 20947488]

[16]
Bao B, Wang Z, Li Y, et al. The complexities of obesity and diabetes with the development and progression of pancreatic cancer. Biochim Biophys Acta  2011; 1815(2): 135-46.
 [PMID: 21129444]

[17]
Noto H, Goto A, Tsujimoto T, Noda M. Cancer risk in diabetic patients treated with metformin: A systematic review and meta-analysis. PLoS One  2012; 7(3): e33411.
 [http://dx.doi.org/10.1371/journal.pone.0033411] [PMID: 22448244]

[18]
Assmann TS, Recamonde-Mendoza M, Puñales M, Tschiedel B, Canani LH, Crispim D. MicroRNA expression profile in plasma from type 1 diabetic patients: Case-control study and bioinformatic analysis. Diabetes Res Clin Pract  2018; 141: 35-46.
 [http://dx.doi.org/10.1016/j.diabres.2018.03.044] [PMID: 29679626]

[19]
Liu L, Yan J, Xu H, et al. Two novel microRNA biomarkers related to β-cell damage and their potential values for early diagnosis of type 1 diabetes. J Clin Endocrinol Metab  2018; 103(4): 1320-9.
 [http://dx.doi.org/10.1210/jc.2017-01417] [PMID: 29370422]

[20]
Jo S, Chen J, Xu G, Grayson TB, Thielen LA, Shalev A. miR-204 controls glucagon-like peptide 1 receptor expression and agonist function. Diabetes  2018; 67(2): 256-64.
 [http://dx.doi.org/10.2337/db17-0506] [PMID: 29101219]

[21]
Xu G, Chen J, Jing G, Grayson TB, Shalev A. miR-204 targets PERK and regulates UPR signaling and β-cell apoptosis. Mol Endocrinol  2016; 30(8): 917-24.
 [http://dx.doi.org/10.1210/me.2016-1056] [PMID: 27384111]

[22]
Mansell A, Smith R, Doyle SL, et al. Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation. Nat Immunol  2006; 7(2): 148-55.
 [http://dx.doi.org/10.1038/ni1299] [PMID: 16415872]

[23]
Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endocr Relat Cancer  2009; 16(4): 1103-23.

[24]
Qin H, Wilson CA, Lee SJ, et al. IFN-β-induced SOCS-1 negatively regulates CD40 gene expression in macrophages and microglia. FASEB J  2006; 20(7): 985-7.
 [http://dx.doi.org/10.1096/fj.05-5493fje] [PMID: 16571771]

[25]
Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis  2017; 76(6): 960-77.
 [http://dx.doi.org/10.1136/annrheumdis-2016-210715] [PMID: 28264816]

[26]
Ungureanu D, Saharinen P, Junttila I, Hilton DJ, Silvennoinen O. Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1. Mol Cell Biol  2002; 22(10): 3316-26.
 [http://dx.doi.org/10.1128/MCB.22.10.3316-3326.2002] [PMID: 11971965]

[27]
Egan PJ, Lawlor KE, Alexander WS, Wicks IP. Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activation. J Clin Invest  2003; 111(6): 915-24.
 [http://dx.doi.org/10.1172/JCI16156] [PMID: 12639998]

[28]
Huang W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res  2009; 37(1): 1-13.
 [http://dx.doi.org/10.1093/nar/gkn923] [PMID: 19033363]

[29]
Kanehisa M, Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res  2000; 28(1): 27-30.
 [http://dx.doi.org/10.1093/nar/28.1.27] [PMID: 10592173]

[30]
Snel B, Lehmann G, Bork P, Huynen MA. STRING: A web-server to retrieve and display the repeatedly occurring neighbourhood of a gene. Nucleic Acids Res  2000; 28(18): 3442-4.
 [http://dx.doi.org/10.1093/nar/28.18.3442] [PMID: 10982861]

[31]
Shannon P, Markiel A, Ozier O, et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res  2003; 13(11): 2498-504.
 [http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]

[32]
Yang C, Peng P, Li L, et al. High expression of GFAT1 predicts poor prognosis in patients with pancreatic cancer. Sci Rep  2016; 6: 39044.
 [http://dx.doi.org/10.1038/srep39044] [PMID: 27996048]

[33]
Ilic M, Ilic I. Epidemiology of pancreatic cancer. World J Gastroenterol  2016; 22(44): 9694-705.
 [http://dx.doi.org/10.3748/wjg.v22.i44.9694] [PMID: 27956793]

[34]
Rahn S, Zimmermann V, Viol F, et al. Diabetes as risk factor for pancreatic cancer: Hyperglycemia promotes epithelial-mesenchymal-transition and stem cell properties in pancreatic ductal epithelial cells. Cancer Lett  2018; 415: 129-50.
 [http://dx.doi.org/10.1016/j.canlet.2017.12.004] [PMID: 29222037]

[35]
Rawla P, Thandra KC, Sunkara T. Pancreatic cancer and obesity: Epidemiology, mechanism, and preventive strategies. Clin J Gastroenterol  2019; 12(4): 285-91.
 [http://dx.doi.org/10.1007/s12328-019-00953-3] [PMID: 30788774]

[36]
Lowenfels AB, Maisonneuve P, Whitcomb DC, Lerch MM, DiMagno EP. Cigarette smoking as a risk factor for pancreatic cancer in patients with hereditary pancreatitis. JAMA  2001; 286(2): 169-70.
 [http://dx.doi.org/10.1001/jama.286.2.169] [PMID: 11448279]

[37]
Tramacere I, Scotti L, Jenab M, et al. Alcohol drinking and pancreatic cancer risk: A meta-analysis of the dose-risk relation. Int J Cancer  2010; 126(6): 1474-86.
 [http://dx.doi.org/10.1002/ijc.24936] [PMID: 19816941]

[38]
Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology  2013; 144(6): 1252-61.
 [http://dx.doi.org/10.1053/j.gastro.2013.01.068] [PMID: 23622135]

[39]
Stolzenberg-Solomon RZ, Blaser MJ, Limburg PJ, et al. ATBC Study. Helicobacter pylori seropositivity as a risk factor for pancreatic cancer. J Natl Cancer Inst  2001; 93(12): 937-41.
 [http://dx.doi.org/10.1093/jnci/93.12.937] [PMID: 11416115]

[40]
Chang CH, Lin JW, Wu LC, Lai MS, Chuang LM, Chan KA. Association of thiazolidinediones with liver cancer and colorectal cancer in type 2 diabetes mellitus. Hepatology  2012; 55(5): 1462-72.
 [http://dx.doi.org/10.1002/hep.25509] [PMID: 22135104]

[41]
Friberg E, Orsini N, Mantzoros C, Wolk A. Diabetes mellitus and risk of endometrial cancer: A meta-analysis. Diabetologia  2007; 51(7): 1365-74.

[42]
Schiel R, Müller UA, Braun A, Stein G, Kath R. Risk of malignancies in patients with insulin-treated diabetes mellitus: Results of a population-based trial with 10-year follow-up (JEVIN). Eur J Med Res  2005; 10(8): 339-44.
 [PMID: 16131475]

[43]
Wolf I, Sadetzki S, Catane R, Karasik A, Kaufman B. Diabetes mellitus and breast cancer. Lancet Oncol  2005; 6(2): 103-11.
 [http://dx.doi.org/10.1016/S1470-2045(05)01736-5] [PMID: 15683819]

[44]
Li D. Diabetes and pancreatic cancer. Mol Carcinog  2012; 51(1): 64-74.
 [http://dx.doi.org/10.1002/mc.20771] [PMID: 22162232]

[45]
Adami H-O, McLaughlin J, Ekbom A, et al. Cancer risk in patients with diabetes mellitus. Cancer Causes Control  1991; 2(5): 307-14.
 [http://dx.doi.org/10.1007/BF00051670] [PMID: 1932543]

[46]
Bergmann U, Funatomi H, Yokoyama M, Beger HG, Korc M. Insulin-like growth factor I overexpression in human pancreatic cancer: Evidence for autocrine and paracrine roles. Cancer Res  1995; 55(10): 2007-11.
 [PMID: 7743492]

[47]
Gong J, Robbins LA, Lugea A, Waldron RT, Jeon CY, Pandol SJ. Diabetes, pancreatic cancer, and metformin therapy. Front Physiol  2014; 5: 426.
 [http://dx.doi.org/10.3389/fphys.2014.00426] [PMID: 25426078]

[48]
Mohammed A, Janakiram NB, Brewer M, et al. Antidiabetic drug metformin prevents progression of pancreatic cancer by targeting in part cancer stem cells and mTOR signaling. Transl Oncol  2013; 6(6): 649-59.
 [http://dx.doi.org/10.1593/tlo.13556] [PMID: 24466367]

[49]
Wang Y, An H, Liu T, Qin C, Sesaki H, Guo S, et al. Metformin improves mitochondrial respiratory activity through activation of AMPK. Cell reports  2019; 29(6): 1511-1523. e5.
 [http://dx.doi.org/10.1016/j.celrep.2019.09.070]

[50]
Karnevi E, Said K, Andersson R, Rosendahl AH. Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells. BMC Cancer  2013; 13(1): 235.
 [http://dx.doi.org/10.1186/1471-2407-13-235] [PMID: 23663483]

[51]
Stenmark H, Olkkonen VM. The rab gtpase family. Genome Biol  2001; 2(5): S3007.
 [http://dx.doi.org/10.1186/gb-2001-2-5-reviews3007] [PMID: 11387043]

[52]
Qin X, Wang J, Wang X, Liu F, Jiang B, Zhang Y. Targeting rabs as a novel therapeutic strategy for cancer therapy. Drug Discov Today  2017; 22(8): 1139-47.
 [http://dx.doi.org/10.1016/j.drudis.2017.03.012] [PMID: 28390930]

[53]
Moyer BD, Allan BB, Balch WE. Rab1 interaction with a GM130 effector complex regulates COPII vesicle cis-Golgi tethering. Traffic  2001; 2(4): 268-76.
 [http://dx.doi.org/10.1034/j.1600-0854.2001.1o007.x] [PMID: 11285137]

[54]
Sugawara T, Kano F, Murata M. Rab2A is a pivotal switch protein that promotes either secretion or ER-associated degradation of (pro)insulin in insulin-secreting cells. Sci Rep  2014; 4(1): 6952.
 [http://dx.doi.org/10.1038/srep06952] [PMID: 25377857]

[55]
Luo M-L, Gong C, Chen C-H, et al. The Rab2A GTPase promotes breast cancer stem cells and tumorigenesis via Erk signaling activation. Cell Rep  2015; 11(1): 111-24.
 [http://dx.doi.org/10.1016/j.celrep.2015.03.002] [PMID: 25818297]

[56]
Kajiho H, Kajiho Y, Frittoli E, et al. RAB2A controls MT1-MMP endocytic and E-cadherin polarized Golgi trafficking to promote invasive breast cancer programs. EMBO Rep  2016; 17(7): 1061-80.
 [http://dx.doi.org/10.15252/embr.201642032] [PMID: 27255086]

[57]
Xie J, Yan Y, Liu F, et al. Knockdown of Rab7a suppresses the proliferation, migration, and xenograft tumor growth of breast cancer cells. Biosci Rep  2019; 39(2): BSR20180480.
 [http://dx.doi.org/10.1042/BSR20180480] [PMID: 29769411]

[58]
Jiang M, Lee JN, Bionaz M, Deng XY, Wang Y. Evaluation of suitable internal control genes for RT-qPCR in yak mammary tissue during the lactation cycle. PLoS One  2016; 11(1): e0147705.
 [http://dx.doi.org/10.1371/journal.pone.0147705] [PMID: 26808329]

[59]
Zaldívar-López S, Rowell JL, Fiala EM, Zapata I, Couto CG, Alvarez CE. Comparative genomics of canine hemoglobin genes reveals primacy of beta subunit delta in adult carnivores. BMC Genomics  2017; 18(1): 141.
 [http://dx.doi.org/10.1186/s12864-017-3513-0] [PMID: 28178945]

[60]
Hu H, Zhu W, Qin J, et al. Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis. Hepatology  2017; 65(2): 515-28.
 [http://dx.doi.org/10.1002/hep.28887] [PMID: 27774669]

[61]
Tang SJ, Ho MY, Cho HC, et al. Phosphoglycerate kinase 1-overexpressing lung cancer cells reduce cyclooxygenase 2 expression and promote anti-tumor immunity in vivo. Int J Cancer  2008; 123(12): 2840-8.
 [http://dx.doi.org/10.1002/ijc.23888] [PMID: 18814280]

[62]
Chen G, Gharib TG, Wang H, et al. Protein profiles associated with survival in lung adenocarcinoma. Proc Natl Acad Sci USA  2003; 100(23): 13537-42.
 [http://dx.doi.org/10.1073/pnas.2233850100] [PMID: 14573703]

[63]
Lay AJ, Jiang X-M, Kisker O, et al. Phosphoglycerate kinase acts in tumour angiogenesis as a disulphide reductase. Nature  2000; 408(6814): 869-73.
 [http://dx.doi.org/10.1038/35048596] [PMID: 11130727]

[64]
Wang S, Lincoln TM, Murphy-Ullrich JE. Glucose downregulation of PKG-I protein mediates increased thrombospondin1-dependent TGF-β activity in vascular smooth muscle cells. Am J Physiol Cell Physiol  2010; 298(5): C1188-97.
 [http://dx.doi.org/10.1152/ajpcell.00330.2009] [PMID: 20164378]

[65]
He L, Zhang X, Huang Y, Yang H, Wang Y, Zhang Z. The characterization of RHEB gene and its responses to hypoxia and thermal stresses in the small abalone Haliotis diversicolor. Comp Biochem Physiol B Biochem Mol Biol  2017; 210: 48-54.
 [http://dx.doi.org/10.1016/j.cbpb.2017.06.001] [PMID: 28625796]

[66]
Ghosh AP, Marshall CB, Coric T, et al. Point mutations of the mTOR-RHEB pathway in renal cell carcinoma. Oncotarget  2015; 6(20): 17895-910.
 [http://dx.doi.org/10.18632/oncotarget.4963] [PMID: 26255626]

[67]
Chen K, Liang B, Zou Z, Han Z, Pan J, Liu A. Construction of recombinant lentiviral vectors containing Rheb gene and its mutant Rheb'D60K gene and their expression in human liver cancer cells. Nan Fang Yi Ke Da Xue Xue Bao  2012; 32(3): 341-4.

[68]
Zheng M, Zang S, Xie L, et al. Rheb phosphorylation is involved in p38-regulated/activated protein kinase-mediated tumor suppression in liver cancer. Oncol Lett  2015; 10(3): 1655-61.
 [http://dx.doi.org/10.3892/ol.2015.3406] [PMID: 26622727]

[69]
Tigli H, Seven D, Tunc M, et al. LKB1 mutations and their correlation with LKB1 and Rheb expression in bladder cancer. Mol Carcinog  2013; 52(8): 660-5.
 [http://dx.doi.org/10.1002/mc.21902] [PMID: 22457270]

[70]
He L, Ren Y, Zheng Q, et al. Fas-associated protein with death domain (FADD) regulates autophagy through promoting the expression of Ras homolog enriched in brain (Rheb) in human breast adenocarcinoma cells. Oncotarget  2016; 7(17): 24572-84.
 [http://dx.doi.org/10.18632/oncotarget.8249] [PMID: 27013580]

[71]
Morran DC, Wu J, Jamieson NB, et al. Australian Pancreatic Cancer Genome Initiative (APGI). Targeting mTOR dependency in pancreatic cancer. Gut  2014; 63(9): 1481-9.
 [http://dx.doi.org/10.1136/gutjnl-2013-306202] [PMID: 24717934]

[72]
Javle MM, Shroff RT, Xiong H, et al. Inhibition of the mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: Results of two phase II studies. BMC Cancer  2010; 10(1): 368.
 [http://dx.doi.org/10.1186/1471-2407-10-368] [PMID: 20630061]

[73]
Logsdon CD, Simeone DM, Binkley C, et al. Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer. Cancer Res  2003; 63(10): 2649-57.
 [PMID: 12750293]

[74]
Crnogorac-Jurcevic T, Missiaglia E, Blaveri E, et al. Molecular alterations in pancreatic carcinoma: Expression profiling shows that dysregulated expression of S100 genes is highly prevalent. The journal of pathology: A journal of the pathological society of great Britain and Ireland  2003; 201(1): 63-74.
 [http://dx.doi.org/10.1002/path.1418]

[75]
Arumugam T, Simeone DM, Van Golen K, Logsdon CD. S100P promotes pancreatic cancer growth, survival, and invasion. Clin Cancer Res  2005; 11(15): 5356-64.
 [http://dx.doi.org/10.1158/1078-0432.CCR-05-0092] [PMID: 16061848]

[76]
Sato N, Fukushima N, Matsubayashi H, Goggins M. Identification of maspin and S100P as novel hypomethylation targets in pancreatic cancer using global gene expression profiling. Oncogene  2004; 23(8): 1531-8.
 [http://dx.doi.org/10.1038/sj.onc.1207269] [PMID: 14716296]

[77]
Yang R, Stöcker S, Schott S, et al. The association between breast cancer and S100P methylation in peripheral blood by multicenter case-control studies. Carcinogenesis  2017; 38(3): 312-20.
 [http://dx.doi.org/10.1093/carcin/bgx004] [PMID: 28426874]

[78]
Shen Z-Y, Fang Y, Zhen L, et al. Analysis of the predictive efficiency of S100P on adverse prognosis and the pathogenesis of S100P-mediated invasion and metastasis of colon adenocarcinoma. Cancer Genet  2016; 209(4): 143-53.
 [http://dx.doi.org/10.1016/j.cancergen.2016.02.002] [PMID: 26975699]

[79]
Chien M-H, Lee W-J, Hsieh F-K, et al. Keap1-Nrf2 interaction suppresses cell motility in lung adenocarcinomas by targeting the S100P protein. Clin Cancer Res  2015; 21(20): 4719-32.
 [http://dx.doi.org/10.1158/1078-0432.CCR-14-2880] [PMID: 26078391]

[80]
Afarideh M, Esteghamati VZ, Ganji M, et al. Associations of serum S100B and S100P with the presence and classification of diabetic peripheral neuropathy in adults with type 2 diabetes: A case-cohort study. Canadian J Diabetes  2019; 43(5): 336-344. e2.

[81]
Gutschner T, Hämmerle M, Eissmann M, et al. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res  2013; 73(3): 1180-9.
 [http://dx.doi.org/10.1158/0008-5472.CAN-12-2850] [PMID: 23243023]

[82]
Gutschner T, Hämmerle M, Diederichs S. MALAT1-a paradigm for long noncoding RNA function in cancer. J Mol Med (Berl)  2013; 91(7): 791-801.
 [http://dx.doi.org/10.1007/s00109-013-1028-y] [PMID: 23529762]

[83]
Yoshimoto R, Mayeda A, Yoshida M, Nakagawa S. MALAT1 long non-coding RNA in cancer. Biochimica et Biophysica Acta (BBA)  2016; 1859(1): 192-9.

[84]
Pang E-J, Yang R, Fu XB, Liu YF. Overexpression of long non- coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer. Tumour Biol  2015; 36(4): 2403-7.
 [http://dx.doi.org/10.1007/s13277-014-2850-8] [PMID: 25481511]

[85]
Liu J-H, Chen G, Dang Y-W, Li C-J, Luo D-Z. Expression and prognostic significance of lncRNA MALAT1 in pancreatic cancer tissues. Asian Pac J Cancer Prev  2014; 15(7): 2971-7.
 [http://dx.doi.org/10.7314/APJCP.2014.15.7.2971] [PMID: 24815433]

[86]
Li L, Chen H, Gao Y, et al. Long noncoding RNA MALAT1 promotes aggressive pancreatic cancer proliferation and metastasis via the stimulation of autophagy. Mol Cancer Ther  2016; 15(9): 2232-43.
 [http://dx.doi.org/10.1158/1535-7163.MCT-16-0008] [PMID: 27371730]

[87]
Biswas S, Thomas AA, Chen S, et al. MALAT1: An epigenetic regulator of inflammation in diabetic retinopathy. Sci Rep  2018; 8(1): 6526.
 [http://dx.doi.org/10.1038/s41598-018-24907-w] [PMID: 29695738]

[88]
Liu J, Yao J, Li X, et al. Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus. Cell Death Dis  2014; 5(10): e1506-e.
 [http://dx.doi.org/10.1038/cddis.2014.466]

[89]
Li X, Zeng L, Cao C, et al. Long noncoding RNA MALAT1 regulates renal tubular epithelial pyroptosis by modulated miR-23c targeting of ELAVL1 in diabetic nephropathy. Exp Cell Res  2017; 350(2): 327-35.
 [http://dx.doi.org/10.1016/j.yexcr.2016.12.006] [PMID: 27964927]

[90]
Hu M, Wang R, Li X, et al. LncRNA MALAT1 is dysregulated in diabetic nephropathy and involved in high glucose-induced podocyte injury via its interplay with β-catenin. J Cell Mol Med  2017; 21(11): 2732-47.
 [http://dx.doi.org/10.1111/jcmm.13189] [PMID: 28444861]

[91]
Wang B, Niu D, Lai L, Ren EC. p53 increases MHC class I expression by upregulating the endoplasmic reticulum aminopeptidase ERAP1. Nat Commun  2013; 4(1): 2359.
 [http://dx.doi.org/10.1038/ncomms3359] [PMID: 23965983]

[92]
Medrano G. Determining the role of ATP6V0E1 of the vacuolar-atpase in regulating neuroblastoma cell survival and differentiation 2018.

[93]
Chang X, Han J, Pang L, Zhao Y, Yang Y, Shen Z. Increased PADI4 expression in blood and tissues of patients with malignant tumors. BMC Cancer  2009; 9(1): 40.
 [http://dx.doi.org/10.1186/1471-2407-9-40] [PMID: 19183436]

[94]
Zhang X, Gamble MJ, Stadler S, et al. Genome-wide analysis reveals PADI4 cooperates with Elk-1 to activate c-Fos expression in breast cancer cells. PLoS Genet  2011; 7(6): e1002112.
 [http://dx.doi.org/10.1371/journal.pgen.1002112] [PMID: 21655091]

[95]
Cheng DD, Li SJ, Zhu B, Zhou SM, Yang QC. EEF1D overexpression promotes osteosarcoma cell proliferation by facilitating Akt-mTOR and Akt-bad signaling. J Exp Clin Cancer Res  2018; 37(1): 50.
 [http://dx.doi.org/10.1186/s13046-018-0715-5] [PMID: 29510727]

[96]
Shenyi W, Qia X, Xin R. Construction of EEF1D stable knockdown human ovarian cancer cells and exploration of its drug sensitivity. Acta Universitatis Medicinalis Anhui  2018; (6): 2.

[97]
Flores IL, Kawahara R, Miguel MC, et al. EEF1D modulates proliferation and epithelial-mesenchymal transition in oral squamous cell carcinoma. Clin Sci (Lond)  2016; 130(10): 785-99.
 [http://dx.doi.org/10.1042/CS20150646] [PMID: 26823560]

[98]
Nagy Z, Kanikevich M, Koach J, Mayoh C, Carter D, Liu T, et al. Alyref is a novel binding partner and co-factor for MYCN-driven oncogenesis in neuroblastoma. AACR 2019.
Cite As
Current Diabetes Reviews

New Association Between Diabetes Mellitus and Pancreatic Cancer

Abstract
