RNA结合蛋白Musashi2在实体瘤中的研究进展

Advances in research of Musashi2 in solid tumors

RNA结合蛋白(RBP)在基因调控过程中扮演着关键的作用,参与RNA的翻译、修饰、剪接和转运等重要生命活动,探索RBP对RNA的具体作用意义重大。多项研究表明RBP的异常表达与多种疾病相关。哺乳动物的Musashi(Msi)家族是一类进化保守且功能强大的RBP,其家族成员Msi1和Msi2在调控干细胞活性和肿瘤发生发展中具有重要的作用,具体为通过绑定并调节mRNA的翻译、稳定性及其下游的细胞信号通路从而调控机体的多种生物学进程,其中Msi2与胚胎的生长发育、肿瘤干细胞的维持、血液系统肿瘤的发展等密切相关,而近年来越来越多的报道证实Msi2在实体性肿瘤发生发展中同样发挥着至关重要的作用,主要影响肿瘤的增殖、侵袭、转移及耐药等。具体机制上Msi2主要涉及Wnt/β-catenin、TGF-β/SMAD3、Akt/mTOR、JAK/STAT和Numb及其相关信号通路(Notch、p53和Hedgehog通路)等信号通路。将Msi2基因作为靶点指导肿瘤治疗的临床前研究目前取得了一些初步的成果。本文就Msi2的分子结构、生理功能、在多种实体瘤的发生发展中的作用以及相关信号通路等方面的最新研究进展进行综述。

RNA binding protein(RBP)plays a key role in gene regulation and participate in RNA translation,modification,splicing,transport and other important biological processes.Studies have shown that abnormal expression of RBP is associated with a variety of diseases.The Musashi(Msi)family of mammals is an evolutionarily conserved and powerful RBP,whose members Msi1 and Msi2 play important roles in the regulation of stem cell activity and tumor development.The Msi family members regulate a variety of biological processes by binding and regulating mRNA translation,stability and downstream cell signaling pathways,and among them,Msi2 is closely related to embryonic growth and development,maintenance of tumor stem cells and development of hematological tumors.Accumulating evidence has shown that Msi2 also plays a crucial role in the development of solid tumors,mainly by affecting the proliferation,invasion,metastasis and drug resistance of tumors,involving Wnt/β-catenin,TGF-β/SMAD3,Akt/mTOR,JAK/STAT,Numb and their related signaling pathways(Notch,p53,and Hedgehog pathway).Preclinical studies of Msi2 gene as a therapeutic target for tumor have achieved preliminary results.This review summarizes the molecular structure,physiological function,role of Msi2 in the development and progression of various solid tumors and the signaling pathways involved.