Identification of Key Target Genes and Pathway Analysis in Nonalcoholic Fatty Liver Disease Via Integrated Bioinformatics Analysis

Overview

Journal Balkan J Med Genet

Publisher Sciendo

Specialty Genetics

Date 2023 Mar 7

PMID 36880036

Authors

X Chen

L Zhang

Y Wang

R Li

M Yang

L Gao

Affiliations

Soon will be listed here.

Abstract

Purpose: This study aimed at exploring the mechanisms underlying nonalcoholic fatty liver disease (NAFLD) and developing new diagnostic biomarkers for nonalcoholic steatohepatitis (NASH).

Methods: The microarray dataset GES83452 was downloaded from the NCBI-GEO database, and the differentially expressed RNAs (DERs) were screened between the NAFLD and non-NAFLD samples of the baseline and 1-year follow-up time point group based on the Limma package.

Results: A total of 561 DERs (268 downregulated and 293 upregulated) were screened in the baseline time point group, and 1163 DERs (522 downregulated and 641 upregulated) were screened in the 1-year follow-up time point group. A total of 74 lncRNA-miRNA pairs and 523 miRNA-mRNA pairs were obtained in order to construct a lncRNA-miRNA-mRNA regulatory network. Subsequently, functional enrichment analysis revealed 28 GO and 9 KEGG pathways in the ceRNA regulatory network. and are involved in the Cytokine-cytokine receptor interaction ( = 1.86E-02), and the is involved in both the insulin signaling pathway ( = 1.79E-02) and the pathways in cancer ( = 2.87E-02).

Conclusion: , , and were the characteristic target genes for NAFLD.

Citing Articles

High-Protein Mulberry Leaves Improve Glucose and Lipid Metabolism via Activation of the PI3K/Akt/PPARα/CPT-1 Pathway.

Shan Z, Zhang H, He C, An Y, Huang Y, Fu W Int J Mol Sci. 2024; 25(16).

PMID: 39201413 PMC: 11354309. DOI: 10.3390/ijms25168726.

Forkhead box O1 in metabolic dysfunction-associated fatty liver disease: molecular mechanisms and drug research.

Sha X, Zou X, Liu S, Guan C, Shi W, Gao J Front Nutr. 2024; 11:1426780.

PMID: 39021599 PMC: 11253077. DOI: 10.3389/fnut.2024.1426780.

Identification of metabolic biomarkers associated with nonalcoholic fatty liver disease.

Jiang H, Hu Y, Zhang Z, Chen X, Gao J Lipids Health Dis. 2023; 22(1):150.

PMID: 37697333 PMC: 10494330. DOI: 10.1186/s12944-023-01911-2.

References

Aller R, de Luis D, Izaola O, Gonzalez Sagrado M, Conde R, Pacheco D . Lys656Asn polymorphism of leptin receptor, leptin levels and insulin resistance in patients with non alcoholic fatty liver disease. Eur Rev Med Pharmacol Sci. 2012; 16(3):335-41. View

Zelber-Sagi S, Lotan R, Shlomai A, Webb M, Harrari G, Buch A . Predictors for incidence and remission of NAFLD in the general population during a seven-year prospective follow-up. J Hepatol. 2012; 56(5):1145-1151. DOI: 10.1016/j.jhep.2011.12.011. View

Braschi B, Denny P, Gray K, Jones T, Seal R, Tweedie S . Genenames.org: the HGNC and VGNC resources in 2019. Nucleic Acids Res. 2018; 47(D1):D786-D792. PMC: 6324057. DOI: 10.1093/nar/gky930. View

Noureddin M, Rinella M . Nonalcoholic Fatty liver disease, diabetes, obesity, and hepatocellular carcinoma. Clin Liver Dis. 2015; 19(2):361-79. PMC: 6658171. DOI: 10.1016/j.cld.2015.01.012. View

Zhang X, Shen J, Man K, Chu E, Yau T, Sung J . CXCL10 plays a key role as an inflammatory mediator and a non-invasive biomarker of non-alcoholic steatohepatitis. J Hepatol. 2014; 61(6):1365-75. DOI: 10.1016/j.jhep.2014.07.006. View

Pan X, Zheng M, Zou T, Liu W, Gu X, Zhang X . The LEPR K109R and Q223R Might Contribute to the Risk of NAFLD: A Meta-Analysis. Curr Mol Med. 2018; 18(2):91-99. DOI: 10.2174/1566524018666180705110412. View

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

Li J, Liu S, Zhou H, Qu L, Yang J . starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2013; 42(Database issue):D92-7. PMC: 3964941. DOI: 10.1093/nar/gkt1248. View

Aizawa M, Inagaki S, Moriyama M, Asano K, Kakehashi M . Modeling the natural history of fatty liver using lifestyle-related risk factors: Effects of body mass index (BMI) on the life-course of fatty liver. PLoS One. 2019; 14(10):e0223683. PMC: 6802837. DOI: 10.1371/journal.pone.0223683. View

10.

Neville L, Mathiak G, Bagasra O . The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily. Cytokine Growth Factor Rev. 1998; 8(3):207-19. DOI: 10.1016/s1359-6101(97)00015-4. View

11.

Kozlitina J, Smagris E, Stender S, Nordestgaard B, Zhou H, Tybjaerg-Hansen A . Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2014; 46(4):352-6. PMC: 3969786. DOI: 10.1038/ng.2901. View

12.

Dong X, Copps K, Guo S, Li Y, Kollipara R, DePinho R . Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. Cell Metab. 2008; 8(1):65-76. PMC: 2929667. DOI: 10.1016/j.cmet.2008.06.006. View

13.

Huang D, Sherman B, Lempicki R . Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2008; 37(1):1-13. PMC: 2615629. DOI: 10.1093/nar/gkn923. View

14.

Paraskevopoulou M, Vlachos I, Karagkouni D, Georgakilas G, Kanellos I, Vergoulis T . DIANA-LncBase v2: indexing microRNA targets on non-coding transcripts. Nucleic Acids Res. 2015; 44(D1):D231-8. PMC: 4702897. DOI: 10.1093/nar/gkv1270. View

15.

An B, Lu L, Yuan C, Xin Y, Xuan S . Leptin Receptor Gene Polymorphisms and the Risk of Non-Alcoholic Fatty Liver Disease and Coronary Atherosclerosis in the Chinese Han Population. Hepat Mon. 2016; 16(4):e35055. PMC: 4888499. DOI: 10.5812/hepatmon.35055. View

16.

Huang Z, Shi J, Gao Y, Cui C, Zhang S, Li J . HMDD v3.0: a database for experimentally supported human microRNA-disease associations. Nucleic Acids Res. 2018; 47(D1):D1013-D1017. PMC: 6323994. DOI: 10.1093/nar/gky1010. View

17.

Liu N, Xu X . MicroRNA in central nervous system trauma and degenerative disorders. Physiol Genomics. 2011; 43(10):571-80. PMC: 3110891. DOI: 10.1152/physiolgenomics.00168.2010. View

18.

Lefebvre P, Lalloyer F, Bauge E, Pawlak M, Gheeraert C, Dehondt H . Interspecies NASH disease activity whole-genome profiling identifies a fibrogenic role of PPARα-regulated dermatopontin. JCI Insight. 2017; 2(13). PMC: 5499370. DOI: 10.1172/jci.insight.92264. View

19.

Sookoian S, Rosselli M, Gemma C, Burgueno A, Fernandez Gianotti T, Castano G . Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: impact of liver methylation of the peroxisome proliferator-activated receptor γ coactivator 1α promoter. Hepatology. 2010; 52(6):1992-2000. DOI: 10.1002/hep.23927. View

20.

Wang L, Cao C, Ma Q, Zeng Q, Wang H, Cheng Z . RNA-seq analyses of multiple meristems of soybean: novel and alternative transcripts, evolutionary and functional implications. BMC Plant Biol. 2014; 14:169. PMC: 4070088. DOI: 10.1186/1471-2229-14-169. View