High throughput microarray analysis of Lncrna-mRNA co-expression network in intrahepatic cholangiocarcinoma
TANG Jintian1 WANG Ruibin2 WANG Boqing1▲
1.Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital, Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830000, China;
2.the Third Clinical Medical College, Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830000, China
Abstract:Objective To explore the co-expression network of long non coding RNA (lncRNA)-messenger RNA (mRNA) in intrahepatic cholangiocarcinoma, and to analyze the function of the differentially expressed lncrnas. Methods From January to June 2017, fresh tissue sample of five patients with cholangiocarcinoma who were resected by hepatobiliary surgery in the Affiliated Cancer Hospital, Xinjiang Medical University were selected. High throughput microarray technology was used to analyze the mRNA and lncRNA differential expression profiles, and to construct the lncRNA-mRNA co-expression network. Top 1 lncRNA with significant difference was selected for mRNA co-expression screening, GO analysis and Pathway analysis. In addition, Top1 lncRNA and its co-expression mRNA were verified in other 30 specimens of intrahepatic cholangiocarcinoma. Results When the screening threshold was P ≤ 0.05 and log2 | Fold Change(FC)| ≥1, 475 differential genes were obtained, including 213 up-regulated mRNA and 262 down regulated mRNA; 438 differential lncRNA were obtained, including 131 up-regulated lncRNA and 307 down regulated lncRNA. Top1 lncRNA was screened as carbamoyl phosphate synthase I-intron transcript 1 (CPS1-IT1). GO analysis and Pathway analysis showed that CPS1-IT1 was associated with 20 biological processes and two cellular functions, involving eight cell signaling pathways. Conclution The mRNA and lncRNA in intrahepatic cholangiocarcinoma form a complex co-expression network and participate in many important biological processes.
[1] Razumilava N,Gores GJ. Classification,Diagnosis,and Management of Cholangiocarcinoma [J]. Clin Gastroenterol Hepatol,2013,11,(1):13-21,e1.
[2] Bosman FT,Carneiro F,Hruban RH,et al. Who classification of tumours of the digestive system [M]. International Agency for Research on Cancer,2010.
[3] Tyson GL,El-Serag HB. Risk factors for cholangiocarcinoma [J]. Hepatology,2011,54(1):173-184.
[4] Gutschner T,Diederichs S. The hallmarks of cancer:A long non-coding rna point of view [J]. RNA Biol,2012,9(6):703-719.
[5] Nie L,Wu HJ,Hsu JM,et al. Long non-coding rnas:Versatile master regulators of gene expression and crucial players in cancer [J]. Am J Transl Res,2012,4(2):127-150.
[6] Spizzo R,Almeida MI,Colombatti A,et al. Long non-coding rnas and cancer:A new frontier of translational research? [J]. Oncogene,2012,31(43):4577-4587.
[7] Tsai MC,Spitale RC,Chang HY. Long intergenic noncoding rnas:New links in cancer progression [J]. Cancer Res,2011,71(1):3-7.
[8] McPherson R,Pertsemlidis A,Kavaslar N,et al. A common allele on chromosome 9 associated with coronary heart disease [J]. Science,2007,316(5830):1488-1491.
[9] Johnson R. Long non-coding rnas in huntington’s disease neurodegeneration [J]. Neurobiol Dis,2012,46(2):245-254.
[10] Tan L,Yu JT,Hu N,et al. Non-coding rnas in alzheimer’s disease [J]. Mol Neurobiol,2013,47(1):382-393.
[11] Su W,Wang Y,Jia X,et al. Comparative proteomic study reveals 17β-HSD13 as a pathogenic protein in nonalcoholic fatty liver disease [J]. Proc Natl Acad Sci USA,2014, 111(31):11437-11442.
[12] Kasapkara ?覶S,Aycan Z,A?觭o■lu E,et al. The variable clinical phenotype of three patients with hepatic glycogen synthase deficiency [J]. J Pediatr Endocrinol Metab,2017,30(4):459-462.
[13] Shen XB,Huang L,Zhang SH,et al. Transcriptional regulation of the apolipoprotein F (ApoF) gene by ETS and C/EBP alpha in hepatoma cells [J]. Biochimie,2015, 112:1-9.
[14] Cui HX,Liu RR,Zhao GP,et al. Identification of differentially expressed genes and pathways for intramuscular fat deposition in pectoralis major tissues of fast-and slow-growing chickens [J]. Bmc Genomics,2012,13(1):213.
[15] Xiaoguang Z,Meirong L,Jingjing Z,et al. Long noncoding rna cps1-it1 suppresses cell proliferation and metastasis in human lung cancer [J]. Oncol Res,2017,25(3):373-380.
[16] Wang TH,Yu CC,Lin YS,et al. Long noncoding rna cps1-it1 suppresses the metastasis of hepatocellular carcinoma by regulating hif-1alpha activity and inhibiting epithelial-mesenchymal transition [J]. Oncotarget,2016, 7(28):43588-43603.
[17] Wang TH,Wu CH,Yeh CT,et al. Melatonin suppresses hepatocellular carcinoma progression via lncrna-cps1-it-mediated hif-1α inactivation [J]. Oncotarget,2017,8(47):82280-82293.
[18] Wang YS,Ma LN,Sun JX,et al. Long non-coding rna cps1-it1 is a positive prognostic factor and inhibits epithelial ovarian cancer tumorigenesis [J]. Eur Rev Med Pharmacol Sci,2017,21(14):3169-3175.
[19] Chen YF,Wang R,Chen XA,et al. Differential Expression Analyses of Wnt Pathway Genes in Breast Cancer Patients with Different BMI [C]. International Conference on Biomedical Engineering and Life Science (BELS),2015:230-235.
[20] Lin E,Kuo PH,Liu YL,et al. Effects of circadian clock genes and health-related behavior on metabolic syndrome in a Taiwanese population:Evidence from association and interaction analysis [J]. PLoS One,2017,12(3):e0173861.
[21] Oishi K,Itoh N. Disrupted daily light-dark cycle induces the expression of hepatic gluconeogenic regulatory genes and hyperglycemia with glucose intolerance in mice [J]. Biochem Biophys Res Commun,2013,432(1):111-115.
[22] Zhong X,Yu J,Frazier K,et al. Circadian Clock Regulation of Hepatic Lipid Metabolism by Modulation of m(6)A mRNA Methylation [J]. Cell Rep,2018,25,(7):1816-1828.
[23] Dyar KA,Hubert MJ,Mir AA,et al. Transcriptional programming of lipid and amino acid metabolism by the skeletal muscle circadian clock [J]. PLoS Biol,2018,16,(8):e2005886.
[24] Wu T,Yang L,Jiang J,et al. Chronic glucocorticoid treatment induced circadian clock disorder leads to lipid metabolism and gut microbiota alterations in rats [J]. Life Sci,2018,192:173-182.
[25] Masri S,Patel VR,Eckel-Mahan KL,et al. Circadian acetylome reveals regulation of mitochondrial metabolic pathways [J]. Proc Natl Acad Sci USA,2013,110(9):3339-3344.