Three isoforms of exosomal circPTGR1 promote hepatocellular carcinoma metastasis via the miR449a/MET pathway

In current study, we found that exosomes derived from cells with high metastatic potential (LM3) enhanced the cell migration and invasion of non-metastatic (HepG2) and low metastatic (97L) potential. RNA profiling revealed that circPTGR1, a circRNA with three isoforms, was specifically expressed in exosomes from 97L and LM3 cells. Compared to patients without tumor metastasis, the level of circPTGR1 in the serum exosomes of those with metastatic cancer was upregulated and was also associated with distant tumor metastasis and advanced tumor stage. The functional analysis demonstrated that knockdown circPTGR1 expression suppressed the migration and invasion capabilities of HepG2 and 97L cells when they were co-cultured with LM3 exosomes. Based on bioinformatics, co-expression analysis, and luciferase assay, we discovered that circPTGR1 functioned as a miRNA sponge that competed with MET to target miR449a. Furthermore, we confirmed that the overexpression of miR449a suppressed the cell’s metastatic capability induced by exosomes.