Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth.

摘要: Hepatocellular carcinoma (HCC) is characterized by a propensity for multifocality, growth local spread, and dysregulation of multiple signaling pathways. These features may be determined the tumoral microenvironment. The potential tumor cells to modulate HCC behavior secreted proteins has been extensively studied. In contrast genetic modulation poorly understood. We investigated role involvement derived nanovesicles capable altering gene expression, their ability cell biological effects in other cells. show that can produce nanovesicles, exosomes, differ both RNA protein content from origin. taken up internalized cells, transmit functional transgene. microRNA these exosomes was examined, subset highly enriched within identified. A combinatorial approach identify targets identified transforming factor β activated kinase-1 (TAK1) as most likely candidate pathway could modulated miRNA. Loss TAK1 implicated hepatocarcinogenesis biologically plausible target inter-cellular modulation. showed expression associated enhance transformed recipient Conclusion: Exosome mediated miRNA transfer an important mechanism communication observations unique potentially contribute intrahepatic metastases or multifocal HCC.