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剪接因子异质核糖核蛋白A2/B1(HNRNPA2B1)与人类及小鼠的寿命相关,并在多个癌症的病程进展中发挥重要的作用.然而,HNRNPA2B1能否在细胞衰老这一与个体衰老和抑制癌症密切相关的生物学过程中发挥作用尚不清楚.本研究发现,HNRNPA2B1在多个癌症体系中呈显著上调表达趋势,而在多个细胞衰老体系中则呈显著下调表达趋势,暗示HNRNPA2B1对细胞衰老和癌症具有潜在调控作用.研究结果显示,在多种癌细胞中稳定敲低HNRNPA2B1均可诱导系列细胞衰老相关表型.分子水平的研究表明,HNRNPA2B1的低表达可导致超过1 000个基因发生显著的可变剪接变化,其中包含与细胞衰老有因果关系的基因.进一步研究发现,转录因子E2F1可调节HNRNPA2B1的表达变化.综上,E2F1-HNRNPA2B1是在癌症发展和细胞衰老中均发挥重要作用的一个通路,通过对该通路的调控,可望从诱导癌细胞衰老的角度为相关癌症的研究及治疗提供新的视角.“,”Splicing factor Heterogeneous Nuclear Ribonucleoprotein A2/B1(HNRNPA2B1)is associated with mouse lifespan and human longevity.It also plays a causal role in cancer development.However,whether it participates in cellular senescence,a biological process that contributes to individual aging and inhibits cancer,remains unknown.Here,we report that HNRNPA2B1 showed significantly increased expression in various cancer types while consistently decreased expression in multiple cellular senescence models.Knocking down HNRNPA2B1 in cancer cells leads to a series of senescence-associated phenotypes.In line with its function as a splicing factor,HNRNPA2B1 downregulation causes alternative splicing changes in over one thousand genes,including those known to have a causal role in senescence.Our results also suggests that the E2F transcription factor 1(E2F1)could regulate the expression of HNRNPA2B1,and E2F1-HNRNPA2B1 may be a new regulatory axis functioning in both cancer and cellular senescence,which might also have potential medical implications for cancer therapies.