An exploration on the involvement of the methyltransferase like 3-m6A‑zinc finger MYM-type containing 1 axis in the progression of liver hepatocellular carcinoma

An existing study has underlined the involvement of Methyltransferase Like 3 (METTL3) and its mediated N6-methyladenosine (m⁶A) modification on zinc finger MYM-type containing 1 (ZMYM1) in cancers, and we aimed to explore their implication in liver hepatocellular carcinoma (LIHC). The levels of METTL3 and ZMYM1 in LIHC cells were gauged via qPCR. The involvement of METTL3 in LIHC progression was explored via assays in vitro and in vivo, and the mechanisms underlying the effects of METTL3 on LIHC were explored via m6A methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) and confocal immunofluorescence assays. METTL3, the m⁶A methyltransferase of interest, expressed relatively higher in LIHC. The promoting effects of METTL3 on LIHC progression were confirmed both in vitro and in vivo, and the relevant mechanisms maybe related to ZMYM1, a target of METTL3. Such effects of METTL3-m⁶A-ZMYM1 axis on the progression of LIHC were confirmed to be related to the inactivation of RAS/ERK/c-FOS pathway and the reduction in E-cadherin expression yet the elevation in N-cadherin and Vimentin expressions, therefore accelerating the metastasis in LIHC. Our study highlighted the possible involvement of METTL3-mediated m⁶A modification in LIHC and explored METTL3-m⁶A-ZMYM1 axis as a possible therapeutic target for the anti-metastatic strategy against LIHC.