Detailed resume of RNA m6A demethylases

N6-Methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA, playing critical role in various bioprocesses. Like other epigenetic modifications, m6A modification can be catalyzed by the methyltransferase complex and erased dynamically to maintain cells homeostasis. Up to now, only two m6A demethylases have been reported, fat mass and obesity-associated protein (FTO) and alkylation protein AlkB homolog 5 (ALKBH5), involving in a wide range of mRNA biological progress, including mRNA shearing, export, metabolism and stability. Furthermore, they participate in many significantly biological signaling pathway, and contribute to the progress and development of cancer along with other diseases. In this review, we focus on the studies about structure, inhibitors development and biological function of FTO and ALKBH5.

ALKBH5 suppresses migration and invasion of human trophoblast cells by inhibiting epithelial-mesenchymal transition / 南方医科大学学报

OBJECTIVE@#To investigate the effects of ALKBH5 on migration, invasion and epithelial-mesenchymal transition (EMT) of human trophoblast cells.@*METHODS@#The expression plasmid of ALKBH5 or a negative control plasmid (ALKBH5-NC) was transfected in human trophoblast HTR-8 /SVneo cells, and the expressions of ALKBH5 mRNA and protein were detected by qRT-PCR and Western blotting. Transwell assay was used to assess the changes in migration and invasion abilities of the trophoblast cells after the transfection. Western blotting was performed to detect the expressions of EMT-related proteins in the cells including vimentin, fibronectin, E-cadherin, N-cadherin, MMP9 and MMP2.@*RESULTS@#ALKBH5 mRNA and protein expressions were significantly higher in ALKBH5 group than in the control group (@*CONCLUSIONS@#ALKBH5 is involved in the pathogenesis of preeclampsia by inhibiting EMT of trophoblast cells and hence reducing their migration and invasion abilities.

ALKBH5 inhibits proliferation of HepG2 and L-02 cells / 军事医学

Objective To investigate the effect of AlkB homologue 5 ( ALKBH5 ) on proliferation, cell cycle, and apoptosis of HepG2 and L-02 cells.Methods Recombinant plasmid vector containing the CDS region of ALKBH5 (pEGFP-C1b-ALKBH5) was stably transfected into HepG2 and L-02 cells.Western blotting was used to detect the expression of green fluonescence protein ( GFP )-ALKBH5.There were two groups in our experiment: GFP-ALKBH5 lentivirus group and GFP lentivirus group.Characteristics, such as proliferation, cell cycle and apoptosis of HepG2 and L-02,were detected through Cell Counting Kit-8 (CCK-8) assay, flow cytometry and clone formation, respectively.Results The result of Western blotting revealed that ALKBH5 was efficiently up-regulated at protein levels.Despite apoptosis, phenotypic analysis revealed that the proliferation and cell phases were significantly inhibited in ALKBH5 overexpressed stable cell strains compared with the control cells (both P<0.05).Conclusion ALKBH5 can restrain fetal liver cell (L-02) and hepatocellular carcinoma cell (HepG2) from proliferating.Taken together, our results strongly suggest that ALKBH5 can play a key role in the generation and progression in HCC as a tumor suppressor.