Abstract
sGlycine 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.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common cancer globally and has a high mortality rate[1,2]
We demonstrated that Glycine decarboxylase (GLDC) upregulation is an independent factor for favorable prognosis of hepatocellular carcinoma (HCC) patients and that GLDC enhances cell autophagy, resulting in inhibition of cell migration and invasiveness in HCC cells
GLDC is an independent prognostic factor for HCC patients Our previous study showed that HCC tumors expressed lower GLDC levels, which was correlated with a poor survival rate of HCC patients in The Cancer Genome Atlas (TCGA) database[20]
Summary
Hepatocellular carcinoma (HCC) is the sixth most common cancer globally and has a high mortality rate[1,2]. Cancer metastasis is still the main reason for the low survival rate of HCC patients[3,4]. Autophagy is an evolutionarily conserved lysosome-mediated process for the quality control of intracellular proteins, lipids, and organelles[5]. The role of autophagy in cancer metastasis is still controversial[6]. There are reports that autophagy promotes tumor progress[7,8,9].
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