Geng Xilin, Geng Zhimin, Li Hui, Zhang Yu, Li Jibin, Chang Hulin
Department of Hepatobiliary Surgery, Shaanxi Provincial People's Hospital, Xi'an, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Liver Int. 2020 Jul;40(7):1756-1769. doi: 10.1111/liv.14440. Epub 2020 Mar 31.
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.
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.
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-κB signalling was found to be involved in the promotion of growth and metastasis by TFB2M in HCC cells.
These findings suggest that TFB2M plays a pivotal oncogenic role in HCC cells through activating ROS-Akt-NF-κB signalling pathway.
人线粒体转录因子B2（TFB2M）是线粒体转录的关键调节因子。我们基于癌症基因组图谱（TCGA）数据的生物信息学分析显示，TFB2M在肝细胞癌（HCC）中异常过表达。然而，TFB2M在肿瘤发生中的功能作用，包括在HCC中的作用，仍未得到探索。
通过qRT-PCR和蛋白质印迹分析评估TFB2M的表达及其临床意义。通过细胞增殖、集落形成、细胞周期、凋亡、迁移和侵袭实验确定TFB2M在HCC中的生物学效应及其潜在机制。
TFB2M在HCC中普遍上调，主要是由于miR101-3p的下调，这与HCC患者的不良生存显著相关。功能实验表明，TFB2M在体外显著促进HCC细胞增殖、迁移和侵袭，同时抑制细胞凋亡，并在体内裸鼠模型中促进异种移植瘤形成和肺转移。机制上，发现活性氧（ROS）生成增加以及随后激活的Akt/NF-κB信号通路参与了TFB2M促进HCC细胞生长和转移的过程。
这些发现表明，TFB2M通过激活ROS-Akt-NF-κB信号通路在HCC细胞中发挥关键的致癌作用。
