Exosome‐transmitted circ_MMP2 promotes hepatocellular carcinoma metastasis by upregulating MMP2

Exosomes released by tumor cells have been recently identified as important determinants of tumor progression. They often carry circular RNAs that are differentially expressed in tumors and may regulate tumorigenesis and metastasis. Here, we showed that supernatant of 97H hepatocellular carcinoma (HCC) cell line could promote metastasis in L02 human liver cells and HCC cell lines. Moreover, we determined that circ_MMP2 (has_circ_0039411) could be delivered by 97H- or LM3 cell-derived exosomes to L02 and HepG2 cell cultures. High expression of circ_MMP2 led to the upregulation of its host gene matrix metallopeptidase 2 (MMP2) via the sponging of miR-136-5p. Rescue assays demonstrated that miR-136-5p and MMP2 were two essential participants in HCC metastasis. Finally, high level of circ_MMP2 or MMP2, as well as low level of miR-136-5p, was correlated with low overall survival of HCC patients. Our study highlights a novel molecular pathway in HCC cell-derived exosomes.