Over-expression of TFB2M facilitates cell growth and metastasis via activating ROS-Akt-NF-B signalling in hepatocellular carcinoma

Background & Aims Human TFB2M (mitochondrial transcription factor B2) is a key regulator of mitochondria transcription. Our bioinformatic analysis based on the cancer genome atlas (TCGA) data revealed an aberrant over-expression of TFB2M in hepatocellular carcinoma (HCC). However, the functional roles of TFB2M in tumourigenesis remains unexplored, including HCC. Methods The expression and clinical significance of TFB2M were evaluated by qRT-PCR and western blot analysis. The biological effects and underlying mechanisms of TFB2M in HCC were determined by cell proliferation, colony formation, cell cycle, apoptosis, migration and invasion assays. Results TFB2M was commonly up-regulated in HCC mainly because of the down-regulation of miR101-3p, which significantly correlated with poor survival of HCC patients. Functional experiments revealed that TFB2M significantly promoted HCC cell proliferation, migration and invasion, while inhibited apoptosis in vitro and promoted xenograft tumourigenesis and lung metastasis in nude mice models in vivo. Mechanistically, increased production of reactive oxygen species (ROS) and subsequently activated Akt/NF-kappa B signalling was found to be involved in the promotion of growth and metastasis by TFB2M in HCC cells. Conclusions These findings suggest that TFB2M plays a pivotal oncogenic role in HCC cells through activating ROS-Akt-NF-kappa B signalling pathway.