AUTHOR=Li Changzheng , Chen Jie , Li Yishan , Wu Binghuo , Ye Zhitao , Tian Xiaobin , Wei Yan , Hao Zechen , Pan Yuan , Zhou Hongli , Yang Keyue , Fu Zhiqiang , Xu Jingbo , Lu Yanan 

TITLE=6-Phosphogluconolactonase Promotes Hepatocellular Carcinogenesis by Activating Pentose Phosphate Pathway

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.753196

DOI=10.3389/fcell.2021.753196

ISSN=2296-634X

ABSTRACT=Hepatocellular carcinoma (HCC) has a poor prognosis due to its rapid development and early metastasis. HCC goes through a series of metabolic reprogramming to meet the demand of rapid proliferation, but how metabolic reprogramming regulates HCC proliferation remains unclear. Here, by analyzing the single-cell sequencing data of the livers of HCC patients and healthy people, we found that 6-Phosphogluconolactonase (PGLS) positive HCC subtype had the differentiate ability. A stage-dependent increase of PGLS in human liver tumors was correlated with poor prognosis in patients with HCC. We further demonstrated that downregulation of PGLS impaired the proliferation, migration and invasion capacity of HCC. Mechanistically, PGLS maintained low ROS level and inhibited ROS-mediated apoptosis to further promote HCC function. Overall, our study reveals PGLS is a key metabolic reprogramming gene for HCC, providing a potential therapeutic strategy for the treatment of HCC.