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Role of Asxl2 in non‑alcoholic steatohepatitis‑related hepatocellular carcinoma developed from diabetes

  • Authors:
    • Zhiqiu Hu
    • Ziping Zhang
    • Fei Teng
    • Jinfeng Feng
    • Xubo Wu
    • Qimeng Chang
  • View Affiliations / Copyright

    Affiliations: Department of Hepatopancreatobiliary Surgery, Minhang Hospital, Fudan University, Shanghai 201199, P.R. China
    Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 101-112
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    Published online on: November 4, 2020
       https://doi.org/10.3892/ijmm.2020.4782
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Abstract

The present study investigated the mechanism(s) of non‑alcoholic steatohepatitis‑related hepatocellular carcinoma (NASH‑HCC) developed from diabetes. Streptozotocin and a high‑fat diet (STZ‑HFD) were used to induce NASH‑HCC in ApoE‑/‑ mice. Mouse liver functions were evaluated by H&E staining, liver/body weight and serum biochemical analysis. The expression levels of inflammation‑associated factors were determined by RT‑qPCR. Gene expression profiles related to molecular functions and pathways of NASH‑HCC were examined by principal component analysis, heatmap, gene ontology and KEGG pathway enrichment analysis. Differentially expressed genes (DEGs) in tumor tissues were confirmed by RT‑qPCR. The expression of Asxl2 in human NASH‑HCC, other HCC tissues and HCC cells was measured by western blot (WB analysis) and RT‑qPCR. For SNU‑182 cells transfected with siAsxl2 or Hep3B cells with Asxl2 overexpression, cell proliferation, cell cycle, migration and invasion were respectively determined by CCK‑8 assays, flow cytometry, wounding healing and Transwell assays. The expression levels of cell metastasis‑ and cycle‑related proteins were determined by WB analysis and RT‑qPCR. NASH‑HCC model mice exhibited tumor protrusion with severe steatosis. The blood glucose concentration, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and low‑density lipoprotein (LDL), total bile acid (TBA) and the levels of interleukin (IL)‑6, tumor necrosis factor (TNF)‑α, glypican 3 (GPC3) and transforming growth factor (TGF)‑β were all increased in NASH‑HCC model mice. DEGs were mainly related to chromosome organization, the cell cycle and the mitogen‑activated kinase (MAPK) pathway. Asxl2 was significantly downregulated in HCC tissues and cells, and this regulated cell growth, migration and invasion. The gene expression pattern, related molecular functions and signaling pathways of NASH‑HCC differed from those of normal liver tissues. Additionally, the downregulation of Asxl2 may play a potential role in development of NASH‑HCC in patients with diabetes.
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Copy and paste a formatted citation
Spandidos Publications style
Hu Z, Zhang Z, Teng F, Feng J, Wu X and Chang Q: Role of Asxl2 in non‑alcoholic steatohepatitis‑related hepatocellular carcinoma developed from diabetes. Int J Mol Med 47: 101-112, 2021.
APA
Hu, Z., Zhang, Z., Teng, F., Feng, J., Wu, X., & Chang, Q. (2021). Role of Asxl2 in non‑alcoholic steatohepatitis‑related hepatocellular carcinoma developed from diabetes. International Journal of Molecular Medicine, 47, 101-112. https://doi.org/10.3892/ijmm.2020.4782
MLA
Hu, Z., Zhang, Z., Teng, F., Feng, J., Wu, X., Chang, Q."Role of Asxl2 in non‑alcoholic steatohepatitis‑related hepatocellular carcinoma developed from diabetes". International Journal of Molecular Medicine 47.1 (2021): 101-112.
Chicago
Hu, Z., Zhang, Z., Teng, F., Feng, J., Wu, X., Chang, Q."Role of Asxl2 in non‑alcoholic steatohepatitis‑related hepatocellular carcinoma developed from diabetes". International Journal of Molecular Medicine 47, no. 1 (2021): 101-112. https://doi.org/10.3892/ijmm.2020.4782
Copy and paste a formatted citation
x
Spandidos Publications style
Hu Z, Zhang Z, Teng F, Feng J, Wu X and Chang Q: Role of Asxl2 in non‑alcoholic steatohepatitis‑related hepatocellular carcinoma developed from diabetes. Int J Mol Med 47: 101-112, 2021.
APA
Hu, Z., Zhang, Z., Teng, F., Feng, J., Wu, X., & Chang, Q. (2021). Role of Asxl2 in non‑alcoholic steatohepatitis‑related hepatocellular carcinoma developed from diabetes. International Journal of Molecular Medicine, 47, 101-112. https://doi.org/10.3892/ijmm.2020.4782
MLA
Hu, Z., Zhang, Z., Teng, F., Feng, J., Wu, X., Chang, Q."Role of Asxl2 in non‑alcoholic steatohepatitis‑related hepatocellular carcinoma developed from diabetes". International Journal of Molecular Medicine 47.1 (2021): 101-112.
Chicago
Hu, Z., Zhang, Z., Teng, F., Feng, J., Wu, X., Chang, Q."Role of Asxl2 in non‑alcoholic steatohepatitis‑related hepatocellular carcinoma developed from diabetes". International Journal of Molecular Medicine 47, no. 1 (2021): 101-112. https://doi.org/10.3892/ijmm.2020.4782
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