Brachyury promotes proliferation and migration of hepatocellular carcinoma via facilitating the transcription of NCAPG2

Hepatocellular carcinoma (HCC) has a poor prognosis because of its limited drug responses in clinical trials. Therefore, it is crucial to clarify the molecular mechanisms of HCC progression to identify new diagnostic markers and therapeutic targets. Here, we report that brachyury, which regulates the gene encoding the non-SMC condensin II complex subunit G2 (NCAPG2), promotes tumorigenesis in HCC. Knockdown of brachyury led to inhibition of cancer progression in vitro and in vivo. Chromatin immunoprecipitation-sequencing data indicated that the oncogene NCAPG2 is a direct target of brachyury. Furthermore, NCAPG2 knockdown inhibited the proliferation and migration of HCC cells and attenuated brachyury-induced tumorigenesis. Overexpression and decreased DNA methylation of NCAPG2 were associated with a poor prognosis, and NCAPG2 was positively correlated with various immune cell infiltrates, cancer-associated fibroblasts, and immune checkpoint molecule expression levels in the tumor microenvironment. Moreover, the effectiveness of immune checkpoint blockade was decreased in the high NCAPG2 expression group. Together, these findings demonstrated a coregulatory effect of the brachyury/NCAPG2 axis during HCC progression.