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MicroRNA-488-3p-loaded engineered exosomes inhibit proliferation, migration and invasion of hepatocellular carcinoma
Huijie Gao1,2, Zhaobin He1,2, Shengbiao Yang1,2
1Department of Hepatobiliary Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Abstract:
SEC61G is an oncogene in hepatocellular carcinoma (HCC), a common malignant tumor worldwide. MicroRNAs (miRNAs) regulation of oncogenes are available therapeutic strategies being investigated in HCC, but the effective miRNA delivery remains a challenge. Here, we investigated the potential therapeutic effects of miRNA-loaded engineered exosomes in patients with HCC. MiRNAs that could bind to SEC61G were screened using Targetscan, and were verified using HepG2 cells viability after transfecting miRNAs mimic. Five miRNAs binding to SEC61G,among which, miR-651-3p and miR-488-3p mimic significantly inhibited HepG2 cells viability (p < 0.05) and decreased SEC61G protein expression. Then, dual-luciferase reporter assay also confirmed SEC61G as a target of miR-488-3p in HCC. After that, miR-488-3p-loaded engineered exosomes (Exo-miR-488-3p) were isolated from the supernatant of 488-3p-overexpressed cells and identified via nanoparticle tracking analysis, transmission electron microscopy and western blot. In vitro experiments showed that exo-miR-488-3p significantly inhibited proliferation, colony formation, migration and invasion of HepG2 cells than corresponding negative control. In addition, Exo-miR-488-3p tended to induce HepG2 cells apoptosis, though this relationship was not statistically significant. In conclusion, exo-miR-488-3p inhibits the malignant cytological activities in HCC, a possible strategy in the treatment of HCC.
Insights
Engineered exosomes carrying miR-488-3p effectively inhibit hepatocellular carcinoma (HCC) cell growth and spread. This study highlights engineered exosomes as a promising delivery method for microRNA-based cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Hepatocellular carcinoma (HCC) is a prevalent malignancy worldwide.
- SEC61G acts as an oncogene in HCC development.
- Effective microRNA (miRNA) delivery for cancer therapy remains a significant challenge.
Purpose of the Study:
- To investigate the therapeutic potential of miRNA-loaded engineered exosomes in HCC.
- To identify specific miRNAs targeting the SEC61G oncogene.
- To evaluate the efficacy of engineered exosomes delivering miR-488-3p in HCC cells.
Main Methods:
- Bioinformatic screening (Targetscan) and cell-based assays to identify miRNAs targeting SEC61G.
- Dual-luciferase reporter assay to confirm target interaction.
- Isolation and characterization of engineered exosomes loaded with miR-488-3p (Exo-miR-488-3p) using nanoparticle tracking analysis, transmission electron microscopy, and western blot.
- In vitro assessment of Exo-miR-488-3p effects on HCC cell proliferation, colony formation, migration, invasion, and apoptosis.
Main Results:
- miR-488-3p was identified as a direct inhibitor of SEC61G in HCC cells.
- Engineered exosomes (Exo-miR-488-3p) successfully delivered miR-488-3p into HCC cells.
- Exo-miR-488-3p significantly suppressed HCC cell proliferation, colony formation, migration, and invasion.
- A trend towards increased apoptosis was observed, although not statistically significant.
Conclusions:
- Engineered exosomes loaded with miR-488-3p demonstrate significant potential in inhibiting malignant activities of HCC cells.
- Exo-miR-488-3p represents a viable strategy for targeted miRNA delivery in HCC treatment.
- Further research is warranted to explore the therapeutic application of Exo-miR-488-3p in HCC.
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