Department of Hepatobiliary Surgery, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.
Cell Death Dis. 2018 Sep 20;9(10):956. doi: 10.1038/s41419-018-0987-x.
Human MTP18 (mitochondrial protein 18 kDa) is a novel nuclear-encoded mitochondrial membrane protein that is involved in controlling mitochondrial fission. Our bioinformatic analysis of TCGA data revealed an aberrant overexpression of MTP18 in hepatocellular carcinoma (HCC). We analyzed its biological effects and prognostic significance in this malignancy.
MTP18 expression was evaluated by qRT-PCR and western blot analysis in 20 paired tumor and peritumor tissues. Clinical impact of MTP18 overexpression was assessed in 156 patients with HCC. The effects of MTP18 knockdown or overexpression on cell growth and metastasis were determined by cell proliferation, colony formation, cell cycle, apoptosis, migration, and invasion assays. Furthermore, the underlying molecular mechanisms by which MTP18 overexpression promoted HCC cell growth and metastasis were explored.
MTP18 was commonly overexpressed in HCC tissues mainly due to the downregulation of miR-125b, which significantly contributed to poor prognosis of HCC patients. Functional experiments revealed that MTP18 promoted both the growth and metastasis of HCC cells by inducing the progression of cell cycle, epithelial to mesenchymal transition (EMT) and production of MMP-9, and suppressing cell apoptosis. Mechanistically, increased mitochondrial fission and subsequent ROS production was found to be involved in the promotion of growth and metastasis by MTP18 in HCC cells.
MTP18 plays a pivotal oncogenic role in hepatocellular carcinogenesis; its overexpression may serve as a novel prognostic factor and a therapeutic target in HCC.
人线粒体蛋白 18（MTP18）是一种新型核编码的线粒体膜蛋白，参与控制线粒体裂变。我们对 TCGA 数据的生物信息学分析显示，肝癌（HCC）中存在 MTP18 的异常过表达。我们分析了其在这种恶性肿瘤中的生物学效应和预后意义。
通过 qRT-PCR 和 Western blot 分析对 20 对肿瘤和肿瘤周围组织中的 MTP18 表达进行评估。在 156 例 HCC 患者中评估 MTP18 过表达的临床影响。通过细胞增殖、集落形成、细胞周期、凋亡、迁移和侵袭测定来确定 MTP18 敲低或过表达对细胞生长和转移的影响。此外，还探索了 MTP18 过表达促进 HCC 细胞生长和转移的潜在分子机制。
MTP18 在 HCC 组织中普遍过表达，主要是由于 miR-125b 的下调，这显著导致 HCC 患者的预后不良。功能实验表明，MTP18 通过诱导细胞周期、上皮间质转化（EMT）和 MMP-9 的产生以及抑制细胞凋亡，促进 HCC 细胞的生长和转移。机制上，发现增加的线粒体裂变和随后的 ROS 产生参与了 MTP18 在 HCC 细胞中的生长和转移促进作用。
MTP18 在肝细胞癌发生中发挥关键致癌作用；其过表达可能成为 HCC 的一种新的预后因素和治疗靶点。
