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Negative feedback of miR-29 family TET1 involves in hepatocellular cancer
Li Li Lin1, Wei Wang, ZhaoYang Hu
1Department of Pharmacology, Wuxi Higher Health Vocational Technology School, No. 305, Xinguang Road, Wuxi, 214028, China.
Abstract:
Primary hepatocellular carcinoma (HCC) is the most common form of liver cancer and is one of the most common malignancies worldwide. Tumor suppressor gene silencing through DNA methylation contributes to cancer formation. The ten-eleven translocations (TET) family of α-ketogluta-rate-dependent dioxygenases catalyzes the sequential oxidation of 5-methylcytosine to 5-hydroxymethyl-cytosine, 5-formylcytosine and 5-carboxylcytosine, leading to eventual DNA demethylation. MicroRNAs are an abundant class of 17-25 nucleotides small noncoding RNAs, identified as important regulators of many diverse biological processes. In this study, we showed that TET1 expression was obviously reduced in the majority of examined HCC tissues. And we further investigated the expression and functional involvement of TET1 in proliferation, migration and invasion, and determined that TET1 may function as a tumor suppressor. MiR-29b was proved to inhibit metastasis through the targeting of TET1, indicating that downregulation of miR-29 may involve in HCC carcinogenesis and progression through potentiation of TET1 expression. Thus, we elucidated the roles of feedback of miR-29-TET1 downregulation in HCC development and suggested a potential target in identification of the prognosis and application of cancer therapy for HCC patients.
Insights
TET1, a tumor suppressor gene, is downregulated in hepatocellular carcinoma (HCC). MiR-29b targets TET1, suggesting miR-29b downregulation contributes to HCC progression and offers a potential therapeutic target.
Area of Science:
- Molecular oncology
- Epigenetics
- Hepatocellular carcinoma (HCC) research
Background:
- Primary hepatocellular carcinoma (HCC) is a prevalent global malignancy.
- DNA methylation-mediated tumor suppressor gene silencing is a key mechanism in cancer development.
- Ten-eleven translocations (TET) enzymes regulate DNA demethylation via 5-methylcytosine oxidation.
Purpose of the Study:
- To investigate the expression and function of TET1 in HCC.
- To explore the relationship between TET1 and microRNA-29b (miR-29b) in HCC.
- To elucidate the role of the miR-29b/TET1 axis in HCC development and progression.
Main Methods:
- Analysis of TET1 expression in HCC tissues.
- Functional assays assessing TET1's role in HCC cell proliferation, migration, and invasion.
- Investigation of miR-29b's regulatory effect on TET1 and its impact on HCC metastasis.
Main Results:
- TET1 expression was significantly reduced in most HCC tissues examined.
- TET1 demonstrated tumor suppressor activity by inhibiting HCC cell proliferation, migration, and invasion.
- MiR-29b was identified as a direct target of TET1, and its downregulation correlated with HCC progression.
Conclusions:
- TET1 functions as a tumor suppressor in HCC, with its expression being downregulated.
- The miR-29b/TET1 feedback loop plays a critical role in HCC carcinogenesis and progression.
- Targeting the miR-29b/TET1 pathway may offer a novel strategy for HCC prognosis and therapy.
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