Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, 28 Guiyi Street, Guiyang, Guizhou, People's Republic of China.
School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
Mol Cell Biochem. 2024 Oct;479(10):2769-2784. doi: 10.1007/s11010-023-04850-9. Epub 2023 Nov 10.
MIA3 (melanoma inhibitory active protein 3)/TANGO1 (Golgi transporter component protein) plays an important role in the initiation, development, and metabolism of cancer. We aimed to explore the role and underlying molecular mechanisms of MIA3/TANGO1 in the growth and migration of hepatoma cells. According to the analysis of The Cancer Genome Atlas (TCGA) database, MIA3 is expressed at higher levels in hepatocellular carcinoma (HCC) tissues than in normal tissues. Real-time quantitative polymerase chain reaction (qRT-PCR), immunohistochemistry, and western blotting were used to detect mRNA and protein expression in HCC tissues and cells. The in vitro function of MIA3 in HCC cells was evaluated using Cell Counting Kit-8 (CCK-8), colony formation, cell migration and invasion, and flow cytometry assays. Hep-G2 cells with MIA3 overexpression were subjected to RNA-seq, and the downstream target gene CHAC1 (glutathione-specific γ-glutamyl cyclotransferase 1) was selected according to the results of the volcano map of gene enrichment. The relationship between MIA3 and CHAC1 was revealed by coimmunoprecipitation and confocal microscopy. MIA3 expression was upregulated in HCC organizations and HCC samples in the TCGA dataset. Knocking out MIA3 inhibited the proliferation, migration, and invasion of Hep-G2 cells and promoted the apoptosis of Hep-G2 cells. Overexpression of MIA3 in Huh7 cells promoted the proliferation, migration, and invasion and suppressed the apoptosis of Huh7 cells. Overexpression of MIA3 promoted the expression of CHAC1 and the degradation of glutathione (GSH), thereby promoting the growth and metastasis of HCC cells. Knocking out MIA3 inhibited the expression of CHAC1 and slowed the degradation of glutathione, thereby inhibiting the growth and metastasis of HCC cells. MIA3 further promotes the growth, metastasis, and invasion of hepatoma cells by binding to the CHAC1 protein and promoting GSH degradation.
MIA3（黑色素瘤抑制活性蛋白 3）/TANGO1（高尔基体转运蛋白成分蛋白）在癌症的发生、发展和代谢中发挥着重要作用。我们旨在探讨 MIA3/TANGO1 在肝癌细胞生长和迁移中的作用及其潜在的分子机制。根据癌症基因组图谱（TCGA）数据库的分析，MIA3 在肝癌（HCC）组织中的表达水平高于正常组织。实时定量聚合酶链反应（qRT-PCR）、免疫组织化学和 Western blot 用于检测 HCC 组织和细胞中的 mRNA 和蛋白表达。使用细胞计数试剂盒-8（CCK-8）、集落形成、细胞迁移和侵袭以及流式细胞术评估 MIA3 在 HCC 细胞中的体外功能。用 MIA3 过表达的 Hep-G2 细胞进行 RNA-seq，根据基因富集火山图的结果选择下游靶基因 CHAC1（谷胱甘肽特异性γ-谷氨酰环转移酶 1）。通过共免疫沉淀和共聚焦显微镜揭示 MIA3 与 CHAC1 之间的关系。在 TCGA 数据集的 HCC 组织和 HCC 样本中，MIA3 的表达上调。敲低 MIA3 抑制 Hep-G2 细胞的增殖、迁移和侵袭，并促进 Hep-G2 细胞的凋亡。在 Huh7 细胞中过表达 MIA3 促进 Huh7 细胞的增殖、迁移和侵袭，抑制 Huh7 细胞的凋亡。MIA3 过表达促进 CHAC1 的表达和谷胱甘肽（GSH）的降解，从而促进 HCC 细胞的生长和转移。敲低 MIA3 抑制 CHAC1 的表达并减缓谷胱甘肽的降解，从而抑制 HCC 细胞的生长和转移。MIA3 通过与 CHAC1 蛋白结合并促进 GSH 降解，进一步促进肝癌细胞的生长、转移和侵袭。
