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ALKBH5 prevents hepatocellular carcinoma progression by post-transcriptional inhibition of PAQR4 in an m6A dependent manner.
- Source :
- Experimental Hematology & Oncology; 1/6/2023, Vol. 12 Issue 1, p1-16, 16p
- Publication Year :
- 2023
-
Abstract
- Background: N6-methyladenosine (m6A) is a prevalent modification of mRNA and is known to play important roles in tumorigenesis in many types of cancer. The function of N6-methyladenosine (m6A) RNA methylation depends on a variety of methyltransferases and demethylases. AlkB homolog 5 (ALKBH5) is a demethylase, and its biological function has not been completely explored in HCC. Results: ALKBH5 is downregulated and has antitumor effects in HCC cells. In addition, Progestin and AdipoQ Receptor 4 (PAQR4) was identified as a downstream target of ALKBH5 based on transcriptome sequencing and validation studies. We found that ALKBH5 decreases PAQR4 mRNA and protein expression in an N6-methyladenosine (m6A)-dependent manner. The study also showed that ALKBH5 changes PAQR4 expression via the m6A reader IGF2BP1. In both in vivo and in vitro experiments, PAQR4 showed a strong association with the development of HCC. Finally, we found that PAQR4 interacts with AKT and enhances PI3K/AKT pathway activation. Conclusions: ALKBH5 inhibits HCC growth by downregulating PAQR4 expression in an m6A-dependent manner, therefore suppressing PI3K/AKT pathway activation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 21623619
- Volume :
- 12
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Experimental Hematology & Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 161190568
- Full Text :
- https://doi.org/10.1186/s40164-022-00370-2