Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma

By G. Lou, Xiuli Song, Fan Yang, Shan-shan Wu, Jing Wang, Zhi Chen, Yanning Liu. Journal of Hematology & Oncology, 2015

659 citations recorded by the source corpus.

BackgroundHepatocellular carcinoma (HCC) displays high resistance to conventional chemotherapy. Considering that microRNA-122 (miR-122) performs an essential function to promote chemosensitivity of HCC cells, an effective vehicle-mediated miR-122 delivery may represent a promising strategy for HCC chemotherapy. An increasing interest is focused on the use of exosomes as biological vehicles for microRNAs (miRNA) transfer. Mesenchymal stem cells (MSCs) are known for their capacity to produce large amounts of exosomes. This study aimed to determine whether adipose tissue-derived MSC (AMSC) exosomes can be used for miR-122 delivery.MethodsAMSCs were transfected with a miR-122 expression plasmid. At 48 h after transfection, AMSC-derived exosomes (122-Exo) were harvested and added to recipient HCC cells. Expression levels of miR-122 in AMSCs, exosomes, and HCC cells were quantified by real-time PCR. The mRNA and protein levels of miR-122-target genes in recipient HCC cells were quantified by real-time PCR and Western blot, respectively. The effects of 122-Exo on cell viability, apoptosis, and cell cycle of HCC cells were evaluated by MTT and flow cytometry analysis. Xenograft models were used to determine whether 122-Exo can sensitize HCC cells to sorafenib in vivo.ResultsData showed that miR-122-transfected AMSC can effectively package miR-122 into secreted exosomes, which can mediate miR-122 communication between AMSCs and HCC cells, thereby rendering cancer cells sensitive to chemotherapeutic agents through alteration of miR-122-target gene expression in HCC cells. Moreover, intra-tumor injection of 122-Exo significantly increased the antitumor efficacy of sorafenib on HCC in vivo.ConclusionsThe findings suggest that the export of miR-122 via AMSC exosomes represents a novel strategy to enhance HCC chemosensitivity.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/55f3d23a8bf844de879c19c0c37c0f89467b8e36

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In Cancer Research

1. M. Qasim
2. Muniyandi Jeyaraj
3. S. Alahari
4. Sangiliyandi Gurunathan
5. M. Kang
6. Jin-Hoi Kim

In Molecular Biology

1. M. Qasim
2. Muniyandi Jeyaraj
3. S. Alahari
4. Sangiliyandi Gurunathan
5. M. Kang
6. Jin-Hoi Kim

Citations in the corpus

• Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance (2019, background): “Exosomes derived from adipose mesenchymal stem cells are used to deliver miR-122 promoted chemosensitivity of the HCC cells [156].”
• Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes (2019, background): “of carcinoma growth and increases chemotherapy sensitivity in mouse xenograft models [279].”