The role of the TOB1 gene in growth suppression of hepatocellular carcinoma
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Published on: April 18, 2025
Sheyu Lin1, Qingfeng Zhu, Yang Xu
1Institutes of Biomedical Sciences and Children's Hospital, Fudan University, Shanghai 200032; ; School of Life Sciences, Nantong University, Nantong 226019, P.R. China.
Abstract:
The TOB1 gene, mapped on 17q21, is a member of the BTG/Tob family. In breast cancer it has been identified as a candidate tumor suppressor gene. However, whether TOB1 is a bona fide tumor suppressor and downregulated in hepatocellular carcinoma (HCC) remains unclear. In addition, whether its expression is regulated through methylation requires investigation. In the present study, we therefore analyzed the expression of TOB1 in HCC and its methylation levels in human HCC and breast cancer. No significant difference in the expression levels of TOB1 was observed between tumor tissues and adjacent normal tissues in HCC. Quantitative methylation analysis by MassArray revealed no significant differences at single CpG sites or in the global promoter region, and all these CpG sites shared a similar methylation pattern in HCC and breast cancer. Moreover, 5-aza-2'-deoxycytidine treatment of three tumor cell lines did not cause elevation of TOB1 mRNA in HepG2 cell lines. Based on these data, we speculate that TOB1 may be a candidate non-tumor suppressor gene in HCC. Furthermore, the clinical outcome was not correlated with TOB1 expression or expression rate. In addition, TOB1 expression or expression rate was not correlated with the overall survival (OS) rates or cumulative recurrence rates. Taken together, we suggest that TOB1 does not act as a tumor suppressor in HCC.
Insights
The TOB1 gene is not a tumor suppressor in hepatocellular carcinoma (HCC). Its expression and methylation patterns in HCC tumors did not differ from normal tissues, suggesting it does not play a suppressive role in liver cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The TOB1 gene, part of the BTG/Tob family, is located on chromosome 17q21.
- TOB1 has been proposed as a candidate tumor suppressor gene in breast cancer.
- Its role and regulation in hepatocellular carcinoma (HCC) remain largely uncharacterized.
Purpose of the Study:
- To investigate the expression levels of TOB1 in HCC tissues compared to adjacent normal tissues.
- To analyze the methylation status of the TOB1 promoter region in HCC and breast cancer.
- To determine if TOB1 functions as a tumor suppressor in HCC and if its expression is epigenetically regulated.
Main Methods:
- Quantitative analysis of TOB1 gene expression in HCC tumor and normal tissues.
- MassArray-based quantitative methylation analysis of the TOB1 promoter in HCC and breast cancer.
- Treatment of HCC cell lines (HepG2) with 5-aza-2'-deoxycytidine to assess methylation-dependent regulation of TOB1 expression.
Main Results:
- No significant difference in TOB1 expression was found between HCC tumor and adjacent normal tissues.
- Quantitative methylation analysis revealed no significant differences in CpG sites or the global promoter region between HCC and breast cancer.
- Treatment with 5-aza-2'-deoxycytidine did not lead to an elevation of TOB1 mRNA in HepG2 cells.
- TOB1 expression or its rate of change did not correlate with clinical outcomes, overall survival, or cumulative recurrence rates in HCC patients.
Conclusions:
- TOB1 does not appear to function as a tumor suppressor gene in hepatocellular carcinoma.
- The expression of TOB1 in HCC is not significantly regulated by promoter methylation.
- TOB1 is unlikely to be a prognostic biomarker for HCC given its lack of correlation with clinical outcomes.
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