More importantly, folate and other intermediate metabolites, like SAM and SAH, in one-carbon metabolism are remarkably decreased in vivo and in vitro when silencing MAT2A. Additionally, we defined the positive correlation between the expression level of VCIP135 and MATIIα in HCC and the enrichment of one-carbon metabolites in cancer tissues compared with that in adjacent tissues. Here, VCPIP1 is linked to hepatocellular carcinoma.