Page 29 - 南京医科大学自然版

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 ·1559 ·

A B
shNC shKIF11⁃1+oe⁃NC shKIF11⁃1+oe⁃PROM1
shNC
shKIF11⁃1+oe⁃NC
HCT116 1 200 ** * ** **
shKIF11⁃1+oe⁃PROM1
Number of cells 800

400
DLD1 0
HCT116 DLD1
500 μm
C D
HCT116 DLD1 shNC
shKIF11⁃1+oe⁃NC
shKIF11⁃1+oe⁃PROM1
shKIF11⁃1+oe⁃PROM1
shKIF11⁃1+oe⁃PROM1
shKIF11⁃1+oe⁃NC shKIF11⁃1+oe⁃NC 1.5 HCT116 DLD1
shNC shNC * * * ** ** ** * **
p⁃AKT 60 kDa Relative protein expression 1.0
AKT 60 kDa 0.5
p⁃PI3K 100 kDa
PI3K 85 kDa 0
GAPDH 36 kDa p⁃PI3K/PI3K p⁃AKT/AKT p⁃PI3K/PI3K p⁃AKT/AKT
A，B：Transwell assay showed that overexpression of PROM1 partially rescued the effect of KIF11 knockdown on cell migration ability（×100，scale
bar=100 μm）. C，D：The effect of the KIF11/PROM1 axis on the expression levels of related proteins in the PI3K/AKT signaling pathway was detected
**
*
by WB. P < 0.05 and P < 0.01（n=3）.
图10 KIF11通过调控PROM1促进CRC迁移
Figure 10 KIF11 promoted CRC migration by regulating PROM1

highly expressed in CRC and promoted CRC prolifera⁃ ly restored the tumor suppressor phenotype induced by
tion and migration. the knockdown of METTL3. METTL3 is one of the ma⁃
Studies have shown that KIF11 up⁃regulation can jor“writer”proteins，which has been shown to have a
lead to centrosome fragmentation and chromosome in⁃ dual function in promoting or suppressing cancers. For
stability through multiple signaling pathways，which example，He et al ［38］ showed that METTL3 was lowly ex⁃
leads to exuberant cell division and proliferation，and pressed in PTC and acted as a suppressor in regulating
promotes the progression of tumors，including lung and neutrophil infiltration；many studies have also indicat⁃
［34- 35］
gastric cancers，and glioblastoma . To explore the ed that METTL3 is highly expressed in CRC tissues
molecular mechanisms by which KIF11 regulates CRC and is strongly associated with poor prognosis. For ex⁃
development，we utilized databases and found that ample，METTL3 promotes CRC development by regu⁃
KIF11 was closely associated with m6A methylation lating the m6A⁃CRB3⁃Hippo axis ［39］ . METTL3 inhibi⁃
modifications. RNA methylation modification is a kind tion suppresses cell growth and survival in CRC via
of modification that widely exists in all types of RNAs， ASNS downregulation ［40］ ；It has also been found that

and its leading role is to control the target protein ex⁃ METTL3 promotes cellular senescence of CRC via
pression by regulating the transcription，stability，and modulation of CDKN2B transcription and mRNA sta⁃
［41］ ［42］
translation efficiency of mRNA. They can regulate the bility . Yang et al reported that METTL3⁃mediated
activity of signaling pathways by acting directly or indi⁃ RanGAP1 recruited YTHDF1 to facilitate the develop⁃
［36- 37］
rectly on key molecules . It was demonstrated that ment of CRC via the MAPK pathway. Similarly，
METTL3 mediated the m6A modification of KIF11 and IGF2BP2 promotes cancer progression by influencing
affected its mRNA stability. Moreover，rescue experi⁃ the stability of downstream targets and post⁃transcrip⁃
ments showed that the overexpression of KIF11 partial⁃ tional regulation. Our study，for the first time，proved