Serum exosomes contain ECRG4 mRNA that suppresses tumor growth via inhibition of genes involved in inflammation, cell proliferation, and angiogenesis. (October 2018) - Mao, Liang
Abstract Esophageal cancer related gene-4 (Ecrg4) has been shown to be a tumor suppressor in many organs. Exosomes are naturally secreted nanosized particles that carry signal molecules including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) among others. Upon internalization, exosomes unload their cargos that in turn modulate the biology of the recipient cells. Mounting evidence has shown that exosomal miRNAs are functional. However, reports that exosomes carry functional mRNAs remain scarce. We found that serum exosomes containECRG 4 open reading frame. To simulate serum exosomalECRG 4, stable cell line expressingECRG 4 was created, from which exosomes were isolated and characterized, and the internalization and the resulting biological effects of exosomalECRG 4 were evaluated. Results showed that serum exosomes contain higher levels ofECRG 4 mRNA in healthy individuals than their cancer counterparts. ExosomalECRG 4 can be internalized and unload the encapsulatedECRG 4 into recipient cells, which subsequently suppressed cell proliferation in vitro, and inhibited tumor growth in a xenograft mouse model. Mechanistically, ECRG 4-containing exosomes, when internalized, suppressed the expression of genes commonly implicated in inflammation, cell proliferation, and angiogenesis. Given that exosome is an ideal vehicle for therapeutics delivery and thatECRG 4 is a tumor suppressor gene, the exosomalECRG 4 can be exploited as a formulation for cancer gene therapy.