The let-7c/HoxB7 axis regulates the cell proliferation, migration and apoptosis in hepatocellular carcinoma
Lijun Cai1, Zhangliu Wang2, Huajun Zheng2
1Department of Gastroenterology, the First Affiliated Hospital of Zhejiang Chinese Medical University.
Abstract:
Ectopic expression of HOX-containing genes is closely related to carcinogenesis, acting as either tumor suppressors or oncogenes. A preliminary bioinformatics analysis showed that HoxB7 is a possible target of let-7c. In this study, we aimed to investigate the relationship between HoxB7 and let-7c in liver carcinogenesis. We found that HoxB7 was upregulated in hepatocellular carcinoma (HCC) tissues and cells and negatively correlated with survival time, whereas let-7c was downregulated and positively correlated with survival time in patients with HCC. Let-7c overexpression suppressed proliferation, migration but promoted cell apoptosis in HCC cells. We validated that HoxB7 is a target of let-7c. Consistently, let-7c overexpression reversed the promotional effects of HoxB7 on proliferation and migration in HCC cells, and increased the cell apoptotic rate reduced by HoxB7. Furthermore, let-7c overexpression reversed the promotional effect of HoxB7 on tumor growth in subcutaneous HCC tumor model. Our data suggest that the let-7c/HoxB7 axis regulates HCC development, which may provide a novel therapeutic strategy for the treatment of HCC.
Insights
The let-7c microRNA suppresses liver cancer by downregulating the oncogene HoxB7. This let-7c/HoxB7 interaction offers a potential new therapeutic strategy for hepatocellular carcinoma (HCC) treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- HOX genes are implicated in carcinogenesis, functioning as oncogenes or tumor suppressors.
- Bioinformatics analysis suggested a potential regulatory relationship between HoxB7 and let-7c.
- HoxB7's role in liver carcinogenesis was not fully elucidated.
Purpose of the Study:
- To investigate the functional relationship between HoxB7 and let-7c in the context of liver carcinogenesis.
- To determine the impact of the let-7c/HoxB7 axis on hepatocellular carcinoma (HCC) progression.
Main Methods:
- Analysis of HoxB7 and let-7c expression in HCC tissues and cells.
- Assessment of let-7c's effect on HCC cell proliferation, migration, and apoptosis.
- Validation of HoxB7 as a direct target of let-7c.
- In vivo studies using a subcutaneous HCC tumor model.
Main Results:
- HoxB7 was upregulated and inversely correlated with survival in HCC patients.
- Let-7c was downregulated and positively correlated with survival in HCC patients.
- Let-7c overexpression inhibited HCC cell proliferation and migration, while promoting apoptosis.
- Let-7c directly targets and downregulates HoxB7, reversing HoxB7's oncogenic effects.
- Let-7c suppressed tumor growth in vivo.
Conclusions:
- The let-7c/HoxB7 axis plays a critical role in regulating HCC development.
- Targeting the let-7c/HoxB7 pathway presents a promising therapeutic strategy for hepatocellular carcinoma.
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