Effect of AU-rich element RNA-binding factor 1 on the level of glypican 3 in hepatocellular carcinoma

Ting ZHANG; Guiwen GUAN; Jing ZHANG; Fengmin LU; Xiangmei CHEN

doi:10.3969/j.issn.1001-5256.2021.05.027

Volume 37 Issue 5

May 2021

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Article Navigation > Journal of Clinical Hepatology > 2021 > 37(5): 1116-1120

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Effect of AU-rich element RNA-binding factor 1 on the level of glypican 3 in hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2021.05.027

Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China

Received Date: 2020-12-21
Accepted Date: 2021-01-18
Published Date: 2021-05-20

Abstract

Abstract

Objective To investigate the effect of AU-rich element RNA-binding factor 1 (AUF1) on glypican 3 (GPC3) in hepatocellular carcinoma (HCC) and its possible mechanism. Methods TCGA-HCC gene expression data were downloaded from Broad Institute Genome Data Analysis Center, and finally 371 HCC tissue samples with different etiologies and 50 adjacent tissue samples were included; LCI-HCC gene expression data were downloaded from GSE14520, and 214 patients with hepatitis B-associated HCC who had follow-up data were enrolled. A total of 35 primary liver cancer samples and corresponding adjacent tissue samples were collected from HCC patients who underwent radical surgery in Henan Provincial Cancer Hospital from 2009 to 2013. Immunohistochemistry was used to measure the protein expression of GPC3 and AUF1 in HCC tissue; Western Blot and qRT-PCR were used to measure the expression of GPC3 after AUF1 knockdown or overexpression in hepatoma cell lines; RNA-binding protein immunoprecipitation and RNA turnover assay were used to investigate the potential mechanism of AUF1 in regulating the expression of GPC3. The t-test was used for comparison of quantitative data between two groups, and the chi-square test was used for comparison of rates between two groups; the Kaplan-Meier method was used for survival analysis after surgery, and the log-rank test was used for comparison of survival rates. Results In TCGA and LCI databases, the expression of GPC3 in HCC tissue was significantly higher than that in adjacent tissue (P < 0.05), and in TCGA database, the high expression of GPC3 was associated with the poor prognosis of HCC patients (P < 0.05). Immunohistochemistry showed that both GPC3 and AUF1 proteins are highly expressed in HCC tissue, with a positive expression rate of 77.1% (27/35) and 74.3% (26/35), respectively. In vitro experiment showed that AUF1 knockdown significantly reduced the expression of GPC3 in HepG2 and Huh-7 cells (P < 0.05), while AUF1 overexpression significantly increased the expression of GPC3 (P < 0.05). AUF1 protein could bind to GPC3 mRNA, and AUF1 knockdown reduced the stability of GPC3 mRNA. Conclusion AUF1 is an important post-transcriptional regulator of the GPC3 gene, and the abnormal high expression of AUF1 and GPC3 may be involved in the development and progression of HCC.
- Carcinoma, Hepatocellular,
- AU-Rich Element RNA-Binding Factor 1,
- Glypican-3

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Effect of AU-rich element RNA-binding factor 1 on the level of glypican 3 in hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2021.05.027

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Effect of AU-rich element RNA-binding factor 1 on the level of glypican 3 in hepatocellular carcinoma

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