Objective:To investigate the biological functions and molecular regulatory mechanisms of kinesin family member 11(KIF11)in colorectal cancer(CRC).Methods:The expression of KIF11 in CRC was examined by qRT⁃PCR and publ...Objective:To investigate the biological functions and molecular regulatory mechanisms of kinesin family member 11(KIF11)in colorectal cancer(CRC).Methods:The expression of KIF11 in CRC was examined by qRT⁃PCR and public databases.Functional assays(CCK⁃8,colony formation,EdU,and Transwell)were employed to evaluate KIF11’s roles in CRC progression.Western blot,RIP⁃qPCR,MeRIP⁃qPCR,and RNA stability assays were performed to elucidate the molecular mechanism of N6⁃methyladenosine(m6A)modification for KIF11.RNA sequencing(RNA⁃seq)and correlation analysis were used to examine the downstream mechanism of KIF11 regulation.Results:KIF11 was highly expressed in CRC and promoted CRC proliferation and migration.Mechanistically,methyltransferase⁃like 3(METTL3)/insulin like growth factor 2 mRNA binding protein 2(IGF2BP2)enhanced KIF11 mRNA stability and expression in an m6A⁃dependent way.Furthermore,by means of the PROM1/PI3K/AKT pathway,KIF11 facilitated the progression of CRC.Conclusion:The m6A modification of KIF11 by METTL3/IGF2BP2 contributes to CRC progression via the PI3K/AKT signaling pathway,highlighting its potential as a prognostic biomarker and therapeutic target.展开更多
N6-methyladenosine(m6A)modification,one of the most prevalent RNA epi-genetic modifications in eukaryotes,constitutes over 60%of all RNA methylation modifications.This dynamic modification regulates RNA processing,mat...N6-methyladenosine(m6A)modification,one of the most prevalent RNA epi-genetic modifications in eukaryotes,constitutes over 60%of all RNA methylation modifications.This dynamic modification regulates RNA processing,maturation,nucleocytoplasmic transport,translation efficiency,phase separation,and sta-bility,thereby linking its dysregulation to diverse physiological and pathological processes.METTL3,a core catalytic component of the methyltransferase complex responsible for m6A deposition,is frequently dysregulated in diseases,including colorectal cancer(CRC).Although METTL3’s involvement in CRC pathogenesis has been documented,its precise molecular mechanisms and functional roles remain incompletely understood.METTL3 mediates CRC progression-encompa-ssing proliferation,invasion,drug resistance,and metabolic reprogramming-through m6A-dependent modulation of both coding RNAs and noncoding RNAs.Its regulatory effects are primarily attributed to interactions with key signaling pathways at multiple stages of CRC development.Emerging evidence highlights METTL3 as a promising biomarker for CRC diagnosis and prognosis,as well as a potential therapeutic target.By synthesizing recent advances in METTL3 research within CRC,this review provides critical insights into novel strategies for clinical diagnosis and targeted therapy.展开更多
基金江苏省卫生健康委员会医学科研重点项目(K2023024)789 Outstanding Talent Program of SAHNMU(789ZYRC202090147)。
文摘Objective:To investigate the biological functions and molecular regulatory mechanisms of kinesin family member 11(KIF11)in colorectal cancer(CRC).Methods:The expression of KIF11 in CRC was examined by qRT⁃PCR and public databases.Functional assays(CCK⁃8,colony formation,EdU,and Transwell)were employed to evaluate KIF11’s roles in CRC progression.Western blot,RIP⁃qPCR,MeRIP⁃qPCR,and RNA stability assays were performed to elucidate the molecular mechanism of N6⁃methyladenosine(m6A)modification for KIF11.RNA sequencing(RNA⁃seq)and correlation analysis were used to examine the downstream mechanism of KIF11 regulation.Results:KIF11 was highly expressed in CRC and promoted CRC proliferation and migration.Mechanistically,methyltransferase⁃like 3(METTL3)/insulin like growth factor 2 mRNA binding protein 2(IGF2BP2)enhanced KIF11 mRNA stability and expression in an m6A⁃dependent way.Furthermore,by means of the PROM1/PI3K/AKT pathway,KIF11 facilitated the progression of CRC.Conclusion:The m6A modification of KIF11 by METTL3/IGF2BP2 contributes to CRC progression via the PI3K/AKT signaling pathway,highlighting its potential as a prognostic biomarker and therapeutic target.
基金Supported by Jiangxi Provincial Natural Science Foundation,No.20242BAB25454the Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular of Ministry of Education of Gannan Medical University,No.XN202013+1 种基金Science and Technology Research Project of Jiangxi Provincial Department of Education,No.GJJ201528Startup Foundation for Advanced Talents of Gannan Medical University,No.QD202124.
文摘N6-methyladenosine(m6A)modification,one of the most prevalent RNA epi-genetic modifications in eukaryotes,constitutes over 60%of all RNA methylation modifications.This dynamic modification regulates RNA processing,maturation,nucleocytoplasmic transport,translation efficiency,phase separation,and sta-bility,thereby linking its dysregulation to diverse physiological and pathological processes.METTL3,a core catalytic component of the methyltransferase complex responsible for m6A deposition,is frequently dysregulated in diseases,including colorectal cancer(CRC).Although METTL3’s involvement in CRC pathogenesis has been documented,its precise molecular mechanisms and functional roles remain incompletely understood.METTL3 mediates CRC progression-encompa-ssing proliferation,invasion,drug resistance,and metabolic reprogramming-through m6A-dependent modulation of both coding RNAs and noncoding RNAs.Its regulatory effects are primarily attributed to interactions with key signaling pathways at multiple stages of CRC development.Emerging evidence highlights METTL3 as a promising biomarker for CRC diagnosis and prognosis,as well as a potential therapeutic target.By synthesizing recent advances in METTL3 research within CRC,this review provides critical insights into novel strategies for clinical diagnosis and targeted therapy.
