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Published on: December 5, 2018
Harnessing HEK293 cell-derived exosomes for hsa-miR-365a-3p delivery: Potential application in hepatocellular
Armita Ghotaslou1, Arezou Azizsoltani1,2, Kaveh Baghaei2,3
1Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Abstract:
Hepatocellular carcinoma (HCC) is the most frequent form of liver malignancy, and curing it is very challenging. Restoring tumor suppressor microRNAs could trigger the initiation of cellular anticancer mechanisms. Exosomes are nanosized biocarriers capable of fusing with cell membranes and delivering their cargo. The main goal of the current study was to explore the potential of human embryonic kidney cells (HEK293) cell-derived exosomes to provide an anticancer therapy based on the restoration of tumor suppressor miR-365a downregulated in HepG2 cells. To accomplish this aim, exosomes were isolated from the HEK293 cell line culture and characterized, enriched by Homo sapiens (hsa) miR-365a-3p mimics. Exosomes enabled an efficient loading and intracellular delivery of hsa-miR-365a mimics, which translated into G0/G1 cell cycle arrest, induction of oxidative stress, reduction of migration capacity, and high apoptosis rate. The findings indicate that the delivery of miR-365a-3p by HEK293-derived exosomes may act as an innovative and effective therapeutic strategy against HCC.
Insights
Human embryonic kidney cell-derived exosomes effectively deliver tumor suppressor miR-365a mimics to liver cancer cells. This novel approach shows promise for hepatocellular carcinoma (HCC) therapy by inducing cell cycle arrest and apoptosis.
Area of Science:
- Oncology
- Biotechnology
- Cell Biology
Background:
- Hepatocellular carcinoma (HCC) is a prevalent and challenging liver malignancy.
- Restoring tumor suppressor microRNAs can activate endogenous anticancer mechanisms.
- Exosomes serve as natural nanocarriers for intercellular cargo delivery.
Purpose of the Study:
- To investigate HEK293 cell-derived exosomes for HCC therapy.
- To restore downregulated tumor suppressor miR-365a in HepG2 cells.
- To evaluate exosome-mediated delivery of miR-365a mimics.
Main Methods:
- Exosomes were isolated and characterized from HEK293 cell cultures.
- Exosomes were enriched with Homo sapiens (hsa) miR-365a-3p mimics.
- The therapeutic effects of exosome-delivered miR-365a mimics were assessed in vitro.
Main Results:
- HEK293 exosomes efficiently loaded and delivered hsa-miR-365a mimics intracellularly.
- Treatment induced G0/G1 cell cycle arrest and oxidative stress in HCC cells.
- Exosomes significantly reduced cancer cell migration and increased apoptosis rates.
Conclusions:
- HEK293-derived exosomes effectively deliver miR-365a-3p mimics.
- This exosome-based delivery system shows potential as an innovative HCC therapy.
- Restoration of miR-365a via exosomes offers a promising therapeutic strategy against liver cancer.
