Fig. 5: SETBP1 acted as an oncogene in MDS, METTL14-m6A-SETBP1 regulated PI3K-AKT signaling pathway in MDS. | Leukemia

Fig. 5: SETBP1 acted as an oncogene in MDS, METTL14-m6A-SETBP1 regulated PI3K-AKT signaling pathway in MDS.

From: The m6A methyltransferase METTL14 promotes cell proliferation via SETBP1-mediated activation of PI3K-AKT signaling pathway in myelodysplastic neoplasms

Fig. 5

A q-PCR analysis of SETBP1 in bone marrow mononuclear cells (BM-MNCs) of MDS patients in our center (A–D) showing higher expression of SETBP1 detected in MDS with BM ≥ 5% compared with MDS with BM < 5% or healthy donors. B SETBP1 expression in MDS with higher-risk (IPSS-R > 3.5), MDS with lower-risk (IPSS-R ≤ 3.5), and healthy donors. C Kaplan–Meier survival analysis showing that MDS patients with high SETBP1 level had shorter OS than MDS patients with low SETBP1 level. D Kaplan–Meier survival analysis of MDS patients in our center showing that MDS patients with high SETBP1 level had shorter LFS than MDS patients with low SETBP1 level. E Western blot showing the knockdown effect of SETBP1 in SETBP1-knockdown MDS-L cells. F CellTiter-LumiTM assay showing that knockdown of SETBP1 significantly inhibited the cell proliferation. **P = 0.002; ***P < 0.001. G The colony formation assay showing that knockdown of SETBP1 obviously inhibited the colony-formation ability. ***P < 0.001. H Flow cytometry showing that knockdown of SETBP1 significantly increased the apoptosis of MDS-L cells. ***P < 0.001. I Flow cytometry showing that knockdown of SETBP1 blocked the cell cycle in G0/G1 phase. ***P < 0.001; *P = 0.017; **P = 0.006. J Western blot showing the overexpression effect of SETBP1 in SETBP1-overexpressing MDS-L cells. K CellTiter-LumiTM assay showing that overexpression of SETBP1 notably promoted the cell proliferation. ***P < 0.001. L The colony formation assay showing that overexpression of SETBP1 significantly enhanced the colony-formation ability. ***P < 0.001. M Western blot showing the protein levels of METTL14 and SETBP1 in the MDS-L cells transduced with indicated lentiviruses. N CellTiter-LumiTM assay showing that restoration of SETBP1 expression partly rescued the inhibition of cell proliferation caused by METTL14 knockdown in MDS-L cells. ***P < 0.001. O The colony formation assay showing that restoration of SETBP1 expression partly rescued the inhibition of colony formation ability caused by METTL14 knockdown in MDS-L cells. ***P < 0.001. P Flow cytometry showing that restoration of SETBP1 expression partly rescued the increase of the apoptosis of MDS-L cells caused by METTL14 knockdown. ***P < 0.001. Q Flow cytometry showing that restoration of SETBP1 expression partly rescued the cell cycle arrest caused by knockdown of METTL14. ***P < 0.001; **P = 0.005 (left), 0.006 (right);*P = 0.020. The differences of gene expressions of MDS patients were compared using Mann-Whitney’s t-test. Error bars of gene expression denoted median ± 95% CI. Kaplan–Meier survival analysis was performed using log-rank test. The experimental data were analyzed with Student’s t-test. Error bars of experimental data denoted mean ± SD of three independent experiments. *P < 0.05; **P < 0.01; ***P < 0.001; N.S No significance.

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