Glycine decarboxylase induces autophagy and is downregulated by miRNA-30d-5p in hepatocellular carcinoma.

Cell Death & Disease
Hao ZhuangYongmei Li

Abstract

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.

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Citations

Dec 7, 2019·Cancers·Francesca FornariCatia Giovannini
Jan 30, 2021·Frontiers in Cell and Developmental Biology·Zhen WeiPing Yi
Feb 25, 2021·Pathology, Research and Practice·Soudeh Ghafouri-FardMohammad Taheri
Nov 7, 2020·Chemical Society Reviews·Siyang Ding, Yuning Hong
Jun 12, 2021·Journal of Experimental & Clinical Cancer Research : CR·Jie ShiGuoan Chen
Jun 20, 2021·Clinics and Research in Hepatology and Gastroenterology·Jinying ZhaoLijia Su

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Methods Mentioned

BETA
ubiquitination
confocal microscopy
transfection
antisense oligonucleotide

Software Mentioned

TargetScan
SPSS17
RNAhybrid
PicTar
microRNA

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