Abstract
Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and one of the prominent causes of cancer mortality, leading to approximately 780,000 deaths per year worldwide. Down-regulation of microRNA-125b (miR-125b) is a prognostic indicator in HCC patients. Conversely, over-expression of miR-125b in HCC cells induces cell cycle arrest, inhibits proliferation, migration and invasion. Extracellular vesicles (EVs) function as intercellular messengers transferring proteins, RNAs, DNAs, carbohydrates, and lipids. Since EVs protect their cargo from degradation, delivery of therapeutic bioactive molecules, in particular miRNAs, through EVs represents an innovative avenue for cancer therapy. In this study, we evaluated a replacement strategy for the treatment of HCC via delivery of EVs secreted from human adipose tissue-derived mesenchymal stromal/medicinal signaling cells (ASCs) genetically modified with a lentiviral vector expressing miR-125b with a specific ExoMotif sequence tag to enhance the loading into extracellular vesicles. In particular, we determined that the delivery of miR-125b-loaded EVs produced in engineered ASCs specifically reduces HCC cell proliferation in vitro modulating a series of miR-125b targets, which belong to the p53 signaling pathway. This proof-of-concept study supports the development of innovative therapeutic strategies for HCC via EV-mediated miRNA delivery.
Highlights
Micro RNAs are a class of approximately 22 nucleotide-long non-coding RNAs predominantly involved in the regulation of target gene expression, mainly at the post transcriptional level [1]
We evaluated the effect on cell proliferation of lentiviral-mediated gene transfer into the human Hepatocellular carcinoma (HCC) cell line Hep G2 of a form of miR-125b containing an ExoMotif tag for Micro RNAs (miRNAs) loading into Extracellular vesicles (EVs) (Figure 2)
Supplementation of ExoMotif-tagged miR-125b containing medium reduced melanoma MeWo cells proliferation (Figure 4b). These results suggest that engineered adipose tissue-derived mesenchymal stromal/medicinal signaling cells (ASCs) can release functional miR-125b in the conditioned medium, which results in an anti-proliferative effect on HCC cells
Summary
Micro RNAs (miRNAs) are a class of approximately 22 nucleotide-long non-coding RNAs predominantly involved in the regulation of target gene expression, mainly at the post transcriptional level [1]. More than 2500 miRNAs have been identified in eukaryotic cells, and they have been shown to play a pivotal role in regulating different physiological and pathological processes including cancer development, metastasis and drug resistance [2]. The International Society for Extracellular Vesicles recommends the generic term “extracellular vesicles” (EVs) to collectively denote vesicles obtained from biological samples or cell culture conditioned medium, regardless of differences in biogenesis and composition [7]. EVs function as intercellular messengers transferring proteins, RNA
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
