miR-129-2-3p binds SEMA4C to regulate HCC development and inhibit the EMT
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Updated: Jun 20, 2025

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Published on: April 18, 2025
Background:
Among primary liver cancers, HCC is the most prevalent. Small noncoding RNAs called miRNAs control the expression of downstream target genes to take part in a variety of physiological and pathological processes, including those related to cancer.
Methods:
miR-129-2-3p and SEMA4C expression levels were assessed using RT-qPCR. The CCK-8, invasion, and wound healing assays were used to confirm the capacity of HCC cells for proliferation, invasion and migration respectively. Serum SEMA4C levels were detected via ELISA. The RIP and dual-luciferase reporter assays were used to confirm the existence of intergenic binding sites. Cell apoptosis assay and cell cycle assay were performed to detect the apoptosis rate and cycle distribution of cells, and WB was performed to detect the protein expression of SEMA4C, RhoA, ROCK1, E-cadherin, N-cadherin, and vimentin. Furthermore, cancer-inhibiting role of miR-129-2-3p were further confirmed by animal tests.
Results:
miR-129-2-3p expression was reduced in HCC tissues and cells. Overexpression of miR-129-2-3p decreased the proliferation, invasion, migration, and EMT in HCC cells, whereas inhibition of miR-129-2-3p had the opposite effects. Our research also showed that SEMA4C was increased in HCC tissues, serum and cells, and that SEMA4C knockdown prevented HCC cell invasion, migration, proliferation, and EMT. Overexpression of SEMA4C reversed the inhibitory effect of miR-129-2-3p on HCC.
Conclusions:
Overall, we discovered that through binding to SEMA4C, miR-129-2-3p regulates HCC cell proliferation, invasion, migration, and EMT.
Insights
MicroRNA-129-2-3p inhibits hepatocellular carcinoma (HCC) by targeting SEMA4C. This finding reveals a new therapeutic target for HCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) is the most common primary liver cancer.
- MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and are involved in various biological processes, including cancer.
Purpose of the Study:
- To investigate the role of miR-129-2-3p in HCC.
- To explore the relationship between miR-129-2-3p and SEMA4C in HCC.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) for miRNA and mRNA expression.
- Cell proliferation, invasion, and migration assays (CCK-8, wound healing, transwell).
- Western blotting (WB), ELISA, RNA immunoprecipitation (RIP), and dual-luciferase reporter assays.
Main Results:
- miR-129-2-3p expression was downregulated in HCC tissues and cells.
- miR-129-2-3p overexpression suppressed HCC cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT).
- SEMA4C was upregulated in HCC and its knockdown inhibited HCC progression; SEMA4C overexpression reversed the effects of miR-129-2-3p.
Conclusions:
- miR-129-2-3p acts as a tumor suppressor in HCC.
- miR-129-2-3p inhibits HCC progression by directly targeting SEMA4C.
- This miRNA-mRNA interaction presents a potential therapeutic strategy for HCC.
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