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第45卷第11期      林书慧,钱萌森,朱 静,等. METTL3介导的KIF11 mRNA m6A修饰通过PI3K/AKT信号通路促进结
                 2025年11月              直肠癌进展[J]. 南京医科大学学报(自然科学版),2025,45(11):1546-1562                  ·1557 ·


                A                                                     B
                                               FMC1   2                    Volcano plot
                                               CENPQ
                                               KLHL5                     40
                                               SYNE2
                                               ITGA9
                                               TOP2A  1
                                               CCNG1
                                               CD164
                                               DYNLT3                    30
                                               ERLIN2
                                               DDAH1  0                                          Signficant
                                               SCN4A                    (FDR)
                                               ATP2B4
                                               FAM117B                   20                       Up(n=114)
                                               SLC16A9
                                               IDI1                                               Down(n=52)
                                               PROM1  -1                -lg
                                               EAPP
                                               FOXC1                     10                       Normal(n=13 262)
                                               RBFOX2
                                               TMEM170B
                                               TTC31
                                               CD9    -2
                                               CDK19                     0
                                               HMCN1
                                               SLC16A7
                                               FAT4                         -5      0      5
                                               SESN3
                                               ARHGAP42
                                               UHMK1                               log2|FC|
                                               P3H2
                                               KIF11
                                               NUSAP1
                                               BTBD8
                                               CXADR
                                               MAN2A1
                                               PIK3R1     C
                                               CLDN2                PI3K⁃Akt signaling pathway  P value P.adjust
                                               SPARC
                                               TMEM132B
                                               DYNC2H1           0.1
                                               MSTRG.18981                                      0.004 5 0.040 5
                                               ENSG00000188223
                                               GLDN               0
                                               ST6GALNAC5
                                               MSTRG.11779     enrichment score  -0.1
                                               MSTRG.18069   Running
                                               MAML2
                                               PEG10            -0.2
                                               ENSG00000285897
                                               GPRASP3          -0.3
                                               MSTRG.11048
                                               ADORA2A
                                               ENSG00000282988
                                               SRCAP
                                               ENSG00000286070
                                               KRT13
                                               CASS4              5
                                               HYPK
                                               SYS1⁃DBNDD2
                                               MSTRG.14704   Ranked  list metric  0
                                               ABCA12
                                               MSTRG.12453       -5
                                               DDIT4
                                               H2AJ
                                               UPP1                             5 000         10 000
                                               CHAC1
                                               RUNDC3A
                                               MON1A                           Rank in ordered dataset
                                               ARTN
                                               PER1
                                               ZC3H12A
                                               EGLN2
                                               MSTRG.13937
                                               PHLDA3     D
                                               GDF15
                                               JUN                   HCT116         DLD1        SW480
                                               H2AC18
                                               H2AC19
                                               H2AC25
                                               HIC2
                                               TRIB3
                                               DUSP8
                                               GADD45B                  shKIF11⁃1  shKIF11⁃2  shKIF11⁃1  shKIF11⁃2
                                               EHD1                                                  oe⁃KIF11
                                               RRAD                                              oe⁃NC
                                               LIN28A               shNC          shNC
                                               MSTRG.15271
                                               SLC25A45
                                               AGAP6
                                               MSTRG.21447   p⁃AKT                                     60 kDa
                                               COL17A1
                                               MRM1
                                               TMEM198
                                               H2BC4          AKT                                      60 kDa
                                               PER2
                                               PLK3
                                               DOT1L
                                               MSTRG.12612
                                               BTG2         p⁃PI3K                                     100 kDa
                                               MSTRG.15887
                                               H2BC12
                                               MSTRG.2295
                                               CDKN1A         PI3K                                     85 kDa
                                               H3C10
                                               DUSP1
                                               TP53I3
                                               MSTRG.181    GAPDH                                      36 kDa
                                               MSTRG.4818
                                               MSTRG.4860
                                               CPA4
                                               KRT15
                                               FOSL1
                                               KRTAP1⁃3
                                               CCDC62
                                               SESN1
                                               ARRDC4          E
                                               MSTRG.16143                        HCT116         DLD1
                                               MSTRG.74
                                               DDIT3
                                               SYP
                                               H1⁃2
                                               ATF3
                                               DYNLT2
                                               ARRDC2
                                               SERPINE1
                                               BHLHE41                           shMETTL3+oe⁃KIF11  shMETTL3+oe⁃KIF11
                                               GPR87                        shMETTL3+oe⁃NC  shMETTL3+oe⁃NC
                                               MSTRG.7894
                                               INPP5D
                                               H2BC21
                                               SESN2                    shNC          shNC
                                               FSD2
                                               CXCL3
                                               FOSB
                                               RGS16             p⁃AKT
                                               KLF11                                             60 kDa
                                               PLK2
                                               H4C15
                                               H2BC5
                                               TNFRSF10C          AKT                            60 kDa
                                               H2AC6
                                               KRT80
                                               IL12A
                                               THAP2             p⁃PI3K                          100 kDa
                                               NECTIN4
                                               AKR1B10
                                               PLA2G4C
                                               KHDC4              PI3K                           85 kDa
                                               MSTRG.3934
                                               MSTRG.180
                                               MSTRG.18390
                                               MSTRG.6453       GAPDH                            36 kDa
                                               MSTRG.10325
                                               PYGM
                                               H2BC26
                                               KLHL41
                                               H2BC11
                                               PRDM1
                                               TNFAIP3
                                               GRHL2
                                               MSTRG.4706
                                               H2BC15
                                               RSRP1
                                               H2BC6
                                               MSTRG.9969
                        NC1  NC2  NC3  S11  S12  S13
                   A:Heatmap of the results of cellular RNA⁃seq analysis. B:Volcano plot of the results of cellular RNA⁃seq analysis. C:GSEA enrichment analysis
                showed that KIF11 was associated with PI3K/AKT signaling pathway. D:The expression level of related proteins in the PI3K/AKT signaling pathway
                after knockdown or overexpression of KIF11 was detected by WB. E:WB was performed to detect the effect of the METTL3/KIF11 axis on the expression
                level of related proteins in the PI3K/AKT signaling pathway(n=3).
                                            图8  KIF11通过PI3K/AKT信号通路促进CRC进展
                               Figure 8 KIF11 promoted CRC progression through the PI3K/AKT signaling pathway
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