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Published on: April 18, 2025
MiR-520b suppresses proliferation of hepatoma cells through targeting ten-eleven translocation 1 (TET1) mRNA
Weiying Zhang1, Zhanping Lu1, Yuen Gao1
1State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin, PR China.
Abstract:
Accumulating evidence indicates that microRNAs are able to act as oncogenes or tumor suppressor genes in human cancer. We previously reported that miR-520b was down-regulated in hepatocellular carcinoma (HCC) and its deregulation was involved in hepatocarcinogenesis. In the present study, we report that miR-520b suppresses cell proliferation in HCC through targeting the ten-eleven translocation 1 (TET1) mRNA. Notably, we identified that miR-520b was able to target 3'-untranslated region (3'UTR) of TET1 mRNA by luciferase reporter gene assays. Then, we revealed that miR-520b was able to reduce the expression of TET1 at the levels of mRNA and protein using reverse transcription-polymerase chain reaction and Western blotting analysis. In terms of function, 5-ethynyl-2-deoxyuridine (EdU) incorporation and colony formation assays demonstrated that the forced miR-520b expression remarkably inhibited proliferation of hepatoma cells, but TET1 overexpression could rescue the inhibition of cell proliferation mediated by miR-520b. Furthermore, anti-miR-520b enhanced proliferation of hepatoma cells, whereas silencing of TET1 abolished anti-miR-520b-induced acceleration of cell proliferation. Then, we validated that the expression levels of miR-520b were negatively related to those of TET1 mRNA in clinical HCC tissues. Thus, we conclude that miR-520b depresses proliferation of liver cancer cells through targeting 3'UTR of TET1 mRNA. Our finding provides new insights into the mechanism of hepatocarcinogenesis.
Insights
MicroRNA 520b suppresses liver cancer cell proliferation by targeting TET1 mRNA. This finding reveals a new mechanism in hepatocellular carcinoma development.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) play crucial roles as oncogenes or tumor suppressors in human cancers.
- Previous research indicated miR-520b downregulation in hepatocellular carcinoma (HCC), suggesting its involvement in hepatocarcinogenesis.
Purpose of the Study:
- To investigate the suppressive role of miR-520b in HCC cell proliferation.
- To identify the target gene of miR-520b and elucidate its mechanism in HCC.
Main Methods:
- Luciferase reporter gene assays to confirm miR-520b targeting of TET1 mRNA.
- Reverse transcription-polymerase chain reaction and Western blotting to assess TET1 expression.
- Cell proliferation assays (EdU incorporation, colony formation) to evaluate functional effects.
- Analysis of clinical HCC tissues to correlate miR-520b and TET1 expression.
Main Results:
- miR-520b directly targets the 3'-untranslated region (3'UTR) of ten-eleven translocation 1 (TET1) mRNA.
- miR-520b significantly reduces TET1 mRNA and protein expression.
- Overexpression of miR-520b inhibits HCC cell proliferation, an effect rescued by TET1 overexpression.
- Inhibition of miR-520b enhances proliferation, which is abolished by TET1 silencing.
- A negative correlation between miR-520b and TET1 mRNA levels was observed in clinical HCC samples.
Conclusions:
- miR-520b acts as a tumor suppressor in HCC by targeting TET1 mRNA.
- This regulatory axis provides novel insights into the molecular mechanisms underlying hepatocarcinogenesis.
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