miR-139-3p/Wnt5A Axis Inhibits Metastasis in Hepatoblastoma
Zhouguang Wu1, Siqi Chen1, Taoyan Zuo1
1Department of General Surgery, Shenzhen Children's Hospital, Yitian Road 7019, Shenzhen, 518000, Guangdong, China.
Abstract:
In order to examine new potential treatment options for the treatment of hepatoblastoma (HB), we identified the differential expression of five-candidate tumor suppressor miRNAs in HB and explored possible regulatory mechanisms of target miRNA molecule. By using real-time quantitative polymerase chain reaction (qPCR), we examined the expression of miRNAs in HB tissues and cells. The effect of has-miR-139-3p mimics on the invasion and migration ability was assessed by transwell assay and scratch-wound assay in HepG2 cells. Subsequently, we analyzed the target genes of miR-139-3p and their enrichment signaling pathways through bioinformatics. qPCR, Western-blot and dual-luciferase assays were further used to assess whether has-miR-139-3p targets Wnt5A. The results showed that hsa-miR-139-3p was significantly decreased in HB cells. Upregulation of hsa-miR-139-3p inhibited the invasive and migratory ability of HepG2. Bioinformatics analysis showed that hsa-miR-139-3p may target Wnt5A to regulate the WNT pathway, which was further confirmed by Western-blot and dual-luciferase assays. Overexpression of Wnt5A can reverse the miR-139-3p mimic-induced declines in the expression of WNT pathway-related proteins and restore the invasion and migration of HepG2. These data indicated that the hsa-miR-139-3p/Wnt5A axis inhibited HB metastasis, suggesting that miR-139-3p and Wnt5A may be potential targets for the treatment of HB.
Insights
Hepatoblastoma (HB) metastasis was inhibited by the tumor suppressor microRNA, hsa-miR-139-3p, which targets Wnt5A. This miR-139-3p/Wnt5A axis presents potential therapeutic targets for HB treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Hepatoblastoma (HB) is a primary liver cancer in children with limited treatment options.
- Identifying novel tumor suppressors and their regulatory mechanisms is crucial for developing effective HB therapies.
Purpose of the Study:
- To investigate the role of hsa-miR-139-3p as a potential tumor suppressor in hepatoblastoma.
- To elucidate the regulatory mechanism of hsa-miR-139-3p and its target in HB metastasis.
Main Methods:
- Quantitative real-time PCR (qPCR) to assess miRNA expression in HB tissues and cells.
- Transwell and scratch-wound assays to evaluate cell invasion and migration.
- Bioinformatic analysis, Western-blot, and dual-luciferase assays to identify and validate miRNA-target interactions and signaling pathways.
Main Results:
- Hsa-miR-139-3p expression was significantly downregulated in HB cells.
- Upregulation of hsa-miR-139-3p suppressed HepG2 cell invasion and migration.
- Hsa-miR-139-3p was confirmed to target Wnt5A, regulating the WNT signaling pathway.
Conclusions:
- The hsa-miR-139-3p/Wnt5A axis plays a critical role in inhibiting HB metastasis.
- Hsa-miR-139-3p and Wnt5A represent promising therapeutic targets for hepatoblastoma treatment.
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