Integration of miRNA-lncRNA-mRNA profiles in liver tissue from EpCAM knockout mice

Authors

  • Zili Lei Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Guangdong TCM Key Laboratory for Metabolic Diseases; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, P.R. China
  • Yuting Lei Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Guangdong TCM Key Laboratory for Metabolic Diseases; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, P.R. China
  • Guibin Chen Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Guangdong TCM Key Laboratory for Metabolic Diseases; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, P.R. China
  • Shaomin Liu 1. Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Guangdong TCM Key Laboratory for Metabolic Diseases; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, P.R. China; 2. School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou 510006, P.R. China
  • Wanwan Liu Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Guangdong TCM Key Laboratory for Metabolic Diseases; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, P.R. China
  • Li Huang 1. Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Guangdong TCM Key Laboratory for Metabolic Diseases; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, P.R. China; 2. School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou 510006, P.R. China
  • Lanxiang Yang 1. Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Guangdong TCM Key Laboratory for Metabolic Diseases; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, P.R. China; 2. School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou 510006, P.R. China
  • Huijuan Wu 1. Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Guangdong TCM Key Laboratory for Metabolic Diseases; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, P.R. China; 2. School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou 510006, P.R. China
  • Yanhong Yang First Affiliated Hospital (School of Clinical Medicine), Guangdong Pharmaceutical University, Guangzhou 510080, P.R. China

DOI:

https://doi.org/10.2298/ABS211207001L

Keywords:

epithelial cell adhesion molecule (EpCAM), metabolism-related gene SET domain bifurcated 2 (Setdb2), miRNA-lncRNA-mRNA regulatory network, mouse liver

Abstract

Paper description:

  • Epithelial cell adhesion molecule (EpCAM) is highly expressed in the liver during development and disease, however, its role in development and liver pathology is unclear.
  • Liver tissues of EpCAM-/- and WT mice at P0 stage were collected for RNA sequencing. Hepatic expression of miRNAs, lncRNAs and mRNAs was confirmed by qPCR.
  • Comprehensive miRNA, lncRNA and mRNA expression profiles in EpCAM-/- mice were established, indicating that EpCAM plays important roles in liver glucose and lipid metabolism.
  • These results will help to elucidate functions and mechanisms of EpCAM in liver development and diseases.

Abstract: The epithelial cell adhesion molecule (EpCAM) is highly expressed in the liver during development and diseases. However, its role in the development and pathology of liver remains to be explored. The liver tissues of EpCAM-/- and wildtype (WT) mice at P0 stage were used for RNA sequencing. The differently expressed miRNAs, lncRNAs and mRNAs were selected and confirmed by qPCR. The expression of metabolism-related gene SET domain bifurcated 2 (Setdb2) was significantly increased in the liver of EpCAM-/- mice; the triglyceride (TG) and total cholesterol (TC) levels in the liver were also markedly decreased in EpCAM-/- mice. The microRNA (miRNA)-long noncoding RNA (lncRNA)-mRNA regulatory networks indicated that EpCAM may play important roles in glucose and lipid metabolism of the liver during development and in disease. The comprehensive miRNA, lncRNA and mRNA expression profiles in the developing liver of EpCAM-/- mice established here might help to elucidate functions and mechanisms of EpCAM during development and in diseases of the liver.

 

Downloads

Download data is not yet available.

References

Lei Z, Maeda T, Tamura A, Nakamura T, Yamazaki Y, Shiratori H, Yashiro K, Tsukita S, Hamada H. EpCAM contributes to formation of functional tight junction in the intestinal epithelium by recruiting claudin proteins. Dev Biol. 2012;371(2):136-45. https://doi.org/10.1016/j.ydbio.2012.07.005

Huang L, Yang Y, Yang F, Liu S, Zhu Z, Lei Z, Guo J. Functions of EpCAM in physiological processes and diseases (Review). Int J Mol Med. 2018;42(4):1771-85. https://doi.org/10.3892/ijmm.2018.3764

Das B, Okamoto K, Rabalais J, Marchelletta RR, Barrett KE, Das S, Niwa M, Sivagnanam M. Congenital tufting enteropathy-associated mutant of epithelial cell adhesion molecule activates the unfolded protein response in a murine model of the disease. Cells. 2020;9(4):946. https://doi.org/10.3390/cells9040946

Das B, Okamoto K, Rabalais J, Kozan PA, Marchelletta RR, McGeough MD, Durali N, Go M, Barrett KE, Das S, Sivagnanam M. Enteroids expressing a disease-associated mutant of EpCAM are a model for congenital tufting enteropathy. Am J Physiol Gastrointest Liver Physiol. 2019;317(5):G580-91. https://doi.org/10.1152/ajpgi.00098.2019

Jiang L, Shen Y, Guo D, Yang D, Liu J, Fei X, Yang Y, Zhang B, Lin Z, Yang F, Wang X, Wang K, Wang J, Cai Z. EpCAM-dependent extracellular vesicles from intestinal epithelial cells maintain intestinal tract immune balance. Nat Commun. 2016;7:13045. https://doi.org/10.1038/ncomms13045

Tanaka M, Okabe M, Suzuki K, Kamiya Y, Tsukahara Y, Saito S, Miyajima A. Mouse hepatoblasts at distinct developmental stages are characterized by expression of EpCAM and DLK1: drastic change of EpCAM expression during liver development. Mech Dev. 2009;126(8-9):665-76. https://doi.org/10.1016/j.mod.2009.06.939

Yousaf M, Tayyeb A, Ali G. Expression profiling of adhesion proteins during prenatal and postnatal liver development in rats. Stem Cells Cloning. 2017;10:21-28. https://doi.org/10.2147/SCCAA.S139497

Mani SKK, Zhang H, Diab A, Pascuzzi PE, Lefrançois L, Fares N, Bancel B, Merle P, Andrisani O. EpCAM-regulated intramembrane proteolysis induces a cancer stem cell-like gene signature in hepatitis B virus-infected hepatocytes. J Hepatol. 2016;65(5):888-98. https://doi.org/10.1016/j.jhep.2016.05.022

Zhou L, Zhu Y. The EpCAM overexpression is associated with clinicopathological significance and prognosis in hepatocellular carcinoma patients: a systematic review and meta-analysis. Int J Surg. 2018;56:274-80. https://doi.org/10.1016/j.ijsu.2018.06.025

Caiment F, Gaj S, Claessen S, Kleinjans J. High-throughput data integration of RNA-miRNA-circRNA reveals novel insights into mechanisms of Benzo[a]pyrene-induced carcinogenicity. Nucleic Acids Res. 2015;43(5):2525-34. https://doi.org/10.1093/nar/gkv115

Chen W, Liu D, Li Q, Zhu H. The function of ncRNAs in rheumatic diseases. Epigenomics. 2019;11(7):821-33. https://doi.org/10.2217/epi-2018-0135

Anastasiadou E, Jacob LS, Slack FJ. Non-coding RNA networks in cancer. Nat Rev Cancer. 2018;18(1):5-18. https://doi.org/10.1038/nrc.2017.99

Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12(12):861-74. https://doi.org/10.1038/nrg3074

Liang H, Yu T, Han Y, Jiang H, Wang C, You T, Zhao X, Shan H, Yang R, Yang L, Shan H, Gu Y. LncRNA PTAR promotes EMT and invasion-metastasis in serous ovarian cancer by competitively binding miR-101-3p to regulate ZEB1 expression. Mol Cancer. 2018;17(1):119. https://doi.org/10.1186/s12943-018-0870-5

Li Y, Huo C, Lin X, Xu J. Computational identification of cross-talking ceRNAs. Adv Exp Med Biol. 2018;1094:97-108. https://doi.org/10.1007/978-981-13-0719-5_10

Yang Y, Liu S, Lei Z, Chen G, Huang L, Yang F, Lei Y, Liu Y, Yang L, Liu W, Lai L, Guo J. Circular RNA profile in liver tissue of EpCAM knockout mice. Int J Mol Med. 2019;44(3):1063-77. https://doi.org/10.3892/ijmm.2019.4270

Langmead B, Salzberg SL. Fast Gapped-Read alignment with Bowtie 2. Nat Methods. 2012;9(4):357-9. https://doi.org/10.1038/nmeth.1923

Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013;14(4):R36. https://doi.org/10.1186/gb-2013-14-4-r36

Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, Pimentel H, Salzberg SL, Rinn JL, Pachter L. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012;7(3):562-78. https://doi.org/10.1038/nprot.2012.016

Tafer H, Hofacker IL. RNAplex: a fast tool for RNA-RNA interaction search. Bioinformatics. 2008;24(22):2657-63. https://doi.org/10.1093/bioinformatics/btn193

Roqueta-Rivera M, Esquejo RM, Phelan PE, Sandor K, Daniel B, Foufelle F, Ding J, Li X, Khorasanizadeh S, Osborne TF. SETDB2 links glucocorticoid to lipid metabolism through Insig2a regulation. Cell Metab. 2016;24(3):474-84. https://doi.org/10.1016/j.cmet.2016.07.025

Choi E, Zhang X, Xing C, Yu H. Mitotic checkpoint regulators control insulin signaling and metabolic homeostasis. Cell. 2016;166(3):567-81. https://doi.org/10.1016/j.cell.2016.05.074

Dollé L, Theise ND, Schmelzer E, Boulter L, Gires O, Grunsven LA. EpCAM and the biology of hepatic stem/progenitor cells. Am J Physiol Gastrointest Liver Physiol. 2015;308(4):G233-50. https://doi.org/10.1152/ajpgi.00069.2014

Matsumoto T, Takai A, Eso Y, Kinoshita K, Manabe T, Seno H, Chiba T, Marusawa H. Proliferating EpCAM-positive ductal cells in the inflamed liver give rise to hepatocellular carcinoma. Cancer Res. 2017;77(22):6131-43. https://doi.org/10.1158/0008-5472.CAN-17-1800

Sancho-Bru P, Altamirano J, Rodrigo-Torres D, Coll M, Millán C, Lozano JJ, Miquel R, Arroyo V, Caballería J, Ginès P, Bataller R. Liver progenitor cell markers correlate with liver damage and predict short-term mortality in patients with alcoholic hepatitis. Hepatology. 2012;55(6):1931-41. https://doi.org/10.1002/hep.25614

Fan H, Zhang H, Pascuzzi PE, Andrisani O. Hepatitis B virus X protein induces EpCAM expression via active DNA demethylation directed by RelA in complex with EZH2 and TET2. Oncogene. 2016;35(6):715-26. https://doi.org/10.1038/onc.2015.122

Gao J, Liu X, Yang F, Liu T, Yan Q, Yang X. By inhibiting Ras/Raf/ERK and MMP-9, knockdown of EpCAM inhibits breast cancer cell growth and metastasis. Oncotarget. 2015;6(29):27187-98. https://doi.org/10.18632/oncotarget.4551

Khosla R, Rastogi A, Ramakrishna G, Pamecha V, Mukhopadhyay A, Vasudevan M, Sarin SK, Trehanpati N. EpCAM+ liver cancer stem-like cells exhibiting autocrine Wnt signaling potentially originate in cirrhotic patients. Stem Cells Transl Med. 2017;6(3):807-18. https://doi.org/10.1002/sctm.16-0248

Ziegler A, Heidenreich R, Braumüller H, Wolburg H, Weidemann S, Mocikat R, Röcken M. EpCAM, a human tumor-associated antigen promotes Th2 development and tumor immune evasion. Blood. 2009;113(15):3494-502. https://doi.org/10.1182/blood-2008-08-175109

Roqueta-Rivera M, Esquejo RM, Phelan PE, Phelan PE, Sandor K, Daniel B, Foufelle F, Ding J, Li X, Khorasanizadeh S, Osborne TF. SETDB2 links glucocorticoid to lipid metabolism through insig2a regulation. Cell Metab. 2016;24(3):474-84. https://doi.org/10.1016/j.cmet.2016.07.025

Yan X, Li W, Yang L, Dong W, Chen W, Mao Y, Xu P, Li D, Yuan H, Li Y. MiR-135a protects vascular endothelial cells against ventilator-induced lung injury by inhibiting PHLPP2 to activate PI3K/Akt pathway. Cell Physiol Biochem. 2018;48(3):1245-58. https://doi.org/10.1159/000492010

Pentimalli F, Forte IM, Esposito L, Indovina P, Iannuzzi CA, Alfano L, Costa C, Barone D, Rocco G, Giordano A. RBL2/p130 is a direct AKT target and is required to induce apoptosis upon AKT inhibition in lung cancer and mesothelioma cell lines. Oncogene. 2018;37(27):3657-71. https://doi.org/10.1038/s41388-018-0214-3

Zhang Z, Wen H, Weng J, Feng L, Liu H, Hu X, Zeng F. Silencing of EPCAM suppresses hepatic fibrosis and hepatic stellate cell proliferation in mice with alcoholic hepatitis via the PI3K/Akt/mTOR signaling pathway. Cell Cycle. 2019;18(18):2239-54. https://doi.org/10.1080/15384101.2019.1642067

Nishio M, Sugimachi K, Goto H, Wang J, Morikawa T, Miyachi Y, Takano Y, Hikasa H, Itoh T, Suzuki SO, Kurihara H, Aishima S, Leask A, Sasaki T, Nakano T, Nishina H, Nishikawa Y, Sekido Y, Nakao K, Shin-Ya K, Mimori K, Suzuki A. Dysregulated YAP1/TAZ and TGF-β signaling mediate hepatocarcinogenesis in Mob1a/1b-deficient mice. Proc Natl Acad Sci U S A. 2016;113(1):E71-80. https://doi.org/10.1073/pnas.1517188113

Jing L, Bo W, Yourong F, Tian W, Shixuan W, Mingfu W. Sema4C mediates EMT inducing chemotherapeutic resistance of miR-31-3p in cervical cancer cells. Sci Rep. 2019;9(1):17727. https://doi.org/10.1038/s41598-019-54177-z

Estep JM, Goodman Z, Sharma H, Younossi E, Elarainy H, Baranova A, Younossi Z. Adipocytokine expression associated with miRNA regulation and diagnosis of NASH in obese patients with NAFLD. Liver Int. 2015;35(4):1367-72. https://doi.org/10.1111/liv.12555

Zhang S, Lin X, Lynn H, Xu G, Li J, Zhao C, Li M. Dietary cholesterol interacts with SREBF1 to modulate obesity in Chinese children. Mol Nutr Food Res. 2017;61(9):1700105. https://doi.org/10.1002/mnfr.201700105

Krause C, Sievert H, Geißler C, Grohs M, Gammal ATE, Wolter S, Ohlei O, Kilpert F, Krämer UM, Kasten M, Klein C, Brabant GE, Mann O, Lehnert H, Kirchner H. Critical evaluation of the DNA-methylation markers ABCG1 and SREBF1 for type 2 diabetes stratification. Epigenomics. 2019;11(8):885-97. https://doi.org/10.2217/epi-2018-0159

Lin Y, Ding D, Huang Q, Liu Q, Lu H, Lu Y, Chi Y, Sun X, Ye G, Zhu H, Wei J, Dong S. Downregulation of miR-192 causes hepatic steatosis and lipid accumulation by inducing SREBF1: novel mechanism for bisphenol A-triggered non-alcoholic fatty liver disease. Biochim Biophys Acta Mol Cell Biol Lipids. 2017;1862(9):869-82. https://doi.org/10.1016/j.bbalip.2017.05.001

Chanprasertyothin S, Jongjaroenprasert W, Ongphiphadhanakul B. The association of soluble IGF2R and IGF2R gene polymorphism with type 2 diabetes. J Diabetes Res. 2015;2015:216383. https://doi.org/10.1155/2015/216383

Puxbaum V, Nimmerfall E, Bäuerl C, Taub N, Blaas P, Wieser J, Mikula M, Mikulits W, Ng KM, Yeoh GCT, Mach L. M6P/IGF2R modulates the invasiveness of liver cells via its capacity to bind mannose 6-phosphate residues. J Hepatol. 2012;57(2):337-43. https://doi.org/10.1016/j.jhep.2012.03.026

Yang X, Yu D, Ren Y, Wei J, Pan W, Zhou C, Zhou L, Liu Y, Yang M. Integrative functional genomics implicates EPB41 dysregulation in hepatocellular carcinoma risk. Am J Hum Genet. 2016;99(2):275-86. https://doi.org/10.1016/j.ajhg.2016.05.029

Downloads

Published

2022-04-01

How to Cite

1.
Lei Z, Lei Y, Chen G, Liu S, Liu W, Huang L, Yang L, Wu H, Yang Y. Integration of miRNA-lncRNA-mRNA profiles in liver tissue from EpCAM knockout mice. Arch Biol Sci [Internet]. 2022Apr.1 [cited 2024Nov.24];74(1):25-39. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/7306

Issue

Vol. 74 No. 1 (2022)

Section

Articles

License

Copyright (c) 2021 Archives of Biological Sciences

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Authors grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.