Fig. 6: METTL14-m⁶A-SETBP1 axis regulated PI3K-AKT pathway in MDS.

A KEGG pathway analysis of m⁶A-hypo and differentially expressed genes upon METTL14 knockdown. B Western blot showing the knockdown of SETBP1 in MDS-L cells led to downregulation of PI3K-AKT signaling pathway. C Western blot showing the overexpression of SETBP1 in MDS-L cells led to upregulation of PI3K-AKT signaling pathway. D Western blot showing the knockdown of METTL14 in MDS-L cells led to reduction of SETBP1 expression and downregulation of PI3K-AKT signaling pathway. E Western blot showing the overexpression of METTL14-WT, but not METTL14-R298P, in MDS-L cells led to promotion of SETBP1 expression and activation of PI3K-AKT signaling pathway. F Western blot showing that the downregulation of PI3K-AKT signaling pathway by METTL14 inhibition was rescued by SETBP1 restoration. G Proposed model depicting the regulation and the role of METTL14 in MDS progression. In MDS cells, METTL14 enhancing SETBP1 mRNA stability and promoting the expression of SETBP1 via increasing m⁶A abundance of SETBP1 transcripts; PI3K-AKT signaling pathway being the downstream of METTL14-m⁶A-SETBP1 to induce MDS tumorigenesis.