Circulating RNA as a novel tumor marker: An in vitro study of the origins and characteristics of extracellular RNA

Many clinical studies have shown that circulating RNA rises in cancer patients, but little is known about the origins of abnormally elevated extracellular RNA (exRNA). We designed four different culture conditions: serum-deprived, hypoxia, low temperature and exposure to an anticancer drug to investigate the origins in vitro. We found in hypoxic culture, exRNA was significantly increased after 48 h compared to control cells. In the other culture models, the amount of exRNA decreased. We also acquired some new characteristics of exRNA by nested PCR: the gene expression of extracellular RNA was significantly lower than the cellular RNA and was resistant to degradation by RNase. Altogether, our results showed that the hypoxia may be responsible for the increased level of circulating RNA and the abnormal metabolic rate of tumor cells is also a potential factor that effects exRNA release. Moreover, it suggests that the exRNA is different from intracellular RNA. Determination of circulating RNA may provide a novel technique for monitoring the efficacy of chemotherapy.