MEF2A promotes the proliferation and angiogenesis of myeloproliferative neoplasm by activating p38 MAPK signaling pathway
The aim of this paper was to investigate the expression of myocyte enhancer factor 2A(MEF2A)gene in myelopro-liferative neoplasm(MPN)and its relation with tumor cell proliferation and angiogenesis.From January 2020 to December 2021,PBMC specimens were collected from 30 healthy volunteers and 60 MPN patients in the Affiliated Hospital of Guilin Medical University.Additionally,MPN tumor cell lines HEL92.1.7(abbreviated HEL),UKE-1,and SET-2 were cultured and used for cellular study.qRT-PCR and western blotting were used to detect the expression levels of MEF2A mRNA and protein.HEL and UKE-1 cells were transfected with MEF2A knock-down or over-expressing plasmid,respectively.Cell viability and monoclonal formation capacity were evaluated by CCK-8 assay and crystal violet staining.Cell apoptosis rate was measured by FACS with Annexin Ⅴ-FITC/PI double staining.The in vitro angiogenic ability was determined by catheter formation assay.The expressions of proteins related to apoptosis,angiogenesis and p38 MAPK signaling pathway were quantified by western blotting.The results showed that the mRNA and protein expressions of MEF2A in PBMCs of MPN patients were significantly higher than those of healthy volunteers(both P＜0.05).The expression levels of MEF2A mRNA and protein in MPN cell lines were also significantly higher than those of PBMCs from healthy controls(all with P＜0.05).In HEL and UKE-1 cell lines,MEF2A over-expression caused increased cell proliferation,clone formation,angiogenesis,and the protein expressions of ANGPT2,FGF1,PDGFA,VEGF,Bcl-2,p-P38,and p-ERK(all with P＜0.05).In contrast,it decreased the cell apoptosis rate and the protein expressions of BAX and cleaved caspase 3(cl-caspase-3)(all with P＜0.05).On the other hand,MEF2A knock-down resulted in the complete opposite effects(all with P＜0.05).In conclusion,MEF2A is broadly distributed in MPN cells at a relatively high level,and knock-down of MEF2A can inhibit the proliferation and angiogenesis while promoting the apoptosis of MPN tumor cells.MEF2A may function by regulating the MAPK signaling pathway.
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