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- Title
TDP-43 upregulates lipid metabolism modulator ABHD2 to suppress apoptosis in hepatocellular carcinoma.
- Authors
Liu, Bo-wen; Wang, Xiang-yun; Cao, Jin-ling; Chen, Lu-lu; Wang, Yi-lei; Zhao, Bing-qian; Zhou, Jia; Shen, Zhi-fa
- Abstract
TAR DNA-Binding Protein 43 (TDP-43) has been well studied in neurodegenerative diseases, but its potential role in malignance is still unclear. Here, we demonstrate that TDP-43 contributes to the suppression of apoptosis by facilitating lipid metabolism in hepatocellular carcinoma (HCC). In HCC cells, TDP-43 is able to suppress apoptosis while deletion of it markedly induces apoptosis. RNA-sequencing identifies the lipid metabolism gene abhydrolase domain containing 2 (ABHD2) as the target gene of TDP-43. Tissue microarray analysis shows the positive correlation of TDP-43 and ABHD2 in HCC. Mechanistically, TDP-43 binds with the UG-rich sequence1 of ABHD2 3'UTR to enhance the mRNA stability of ABHD2, thereby upregulating ABHD2. Afterwards, TDP-43 promotes the production of free fatty acid and fatty acid oxidation-originated reactive oxygen species (ROS) in an ABHD2-dependent manner, so as to suppress apoptosis of HCC. Our findings provide insights into the mechanism of HCC progression and reveal TDP-43/ABHD2 as potential targets for the precise treatment of HCC. TDP-43 acts as an RNA-binding protein that regulates the RNA stability of ABHD2 and affects the release of fatty acids and ROS, which in turn regulates apoptosis and affects the growth of liver tumors.
- Subjects
HEPATOCELLULAR carcinoma; FREE fatty acids; APOPTOSIS; DNA-binding proteins; REACTIVE oxygen species; LIPID metabolism; RNA metabolism; HYDROLASES
- Publication
Communications Biology, 2022, Vol 5, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-022-03788-w