Department of Hepatic Biliary Pancreatic Surgery, Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, 450000, Henan Province, China.
Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.
Cell Death Dis. 2019 Feb 25;10(3):192. doi: 10.1038/s41419-019-1446-z.
Glycine decarboxylase (GLDC) belongs to the glycine cleavage system and is involved in one-carbon metabolism. We previously reported that GLDC downregulation enhances hepatocellular carcinoma (HCC) progression and intrahepatic metastasis through decreasing ROS-mediated ubiquitination of cofilin. The role of autophagy in cancer metastasis is still controversial. Redox-dependent autophagy largely relies on the magnitude and the rate of ROS generation. Thus, we aimed to explore the role of GLDC in cellular autophagy during HCC progression. We showed that a high GLDC expression level is associated with better overall survival and is an independent factor for the favorable prognosis of HCC patients. GLDC overexpression significantly induced cell autophagy, whereas GLDC downregulation reduced cell autophagy. Of note, GLDC is the post-transcriptional target of miR-30d-5p. GLDC overexpression could rescue miR-30d-5p-mediated cell metastasis and increase autophagy. Furthermore, upregulation of GLDC could significantly decrease p62 expression and impair intrahepatic metastasis in vivo. Taken together, our results suggest that GLDC may play an important role to increasing miR-30d-5p-reduced autophagy to suppress HCC progress.
甘氨酸脱羧酶（GLDC）属于甘氨酸裂解系统，参与一碳代谢。我们之前的研究报道表明，GLDC 下调通过降低 ROS 介导的原肌球蛋白去泛素化，增强肝细胞癌（HCC）的进展和肝内转移。自噬在癌症转移中的作用仍存在争议。依赖氧化还原的自噬在很大程度上依赖于 ROS 生成的幅度和速率。因此，我们旨在探索 GLDC 在 HCC 进展过程中细胞自噬中的作用。我们发现高 GLDC 表达水平与更好的总生存率相关，是 HCC 患者预后良好的独立因素。GLDC 过表达显著诱导细胞自噬，而 GLDC 下调则减少细胞自噬。值得注意的是，GLDC 是 miR-30d-5p 的转录后靶标。GLDC 过表达可以挽救 miR-30d-5p 介导的细胞转移并增加自噬。此外，上调 GLDC 可显著降低 p62 表达并损害体内肝内转移。综上所述，我们的研究结果表明，GLDC 可能通过增加 miR-30d-5p 降低的自噬来抑制 HCC 进展，从而发挥重要作用。
