SPIN1与恶性肿瘤  

SPIN1 and malignant tumors

作　　者：肖瑶(综述) 吕蓓蓓(审校) XIAO Yao;LÜBeibei(Department of Pathology,Affiliated Provincial Hospital of Shandong First Medical University,Jinan 250021;Department of Pathology,Affiliated Provincial Hospital of Shandong University,Jinan 250021,China)

机构地区：[1]山东第一医科大学附属省立医院病理科,济南250021 [2]山东大学附属省立医院病理科,济南250021

出　　处：《临床与病理杂志》2023年第12期2158-2163,共6页Journal of Clinical and Pathological Research

基　　金：国家自然科学基金(82103490);山东省自然科学基金(ZR2021MH382)。

摘　　要：SPIN1(spindlin 1)是一种组蛋白修饰阅读器蛋白,通过识别组蛋白H3第4位赖氨酸三甲基化(trimethylation of lysine 4 on histone H3 protein subunit,H3K4me3)促进核糖体RNA的表达,从而影响表观遗传的调控,以此发挥其生物学作用。SPIN1在多种恶性肿瘤中过表达,可受多种长链非编码RNA(long non-coding RNA,lncRNA)、微RNA(microRNA,miRNA)及环状RNA(circularRNA,circRNA)的负向调控,并可由转录因子腺病毒E2因子1(adenovirus E2 factor 1,E2F1)转录激活,通过Wnt、磷脂酰肌醇3激酶/蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B,PI3K/Akt)、转染过程重排(rearrangement during transfection,RET)因子、鼠双微体基因-p53(murine double minute 2-p53,MDM2-p53)等与肿瘤发生相关的信号通路,促进肿瘤的发生、发展,并与不良预后密切相关。随着对SPIN1的研究越来越深入,发现SPIN1可作为多种恶性肿瘤治疗的潜在靶点。目前已开发出针对SPIN1和H3K4me3间相互作用的抑制剂,以此阻断SPIN1的致癌能力。SPIN1(spindlin 1)is a histone-modified reader protein that promotes the expression of ribosome RNA by recognizing trimethylation of lysine 4 on histone H3 protein subunit(H3K4me3),thereby influencing epigenetic regulation and exerting its biological function.SPIN1 is overexpressed in various malignant tumors and can be negatively regulated by various long non-coding RNAs(lncRNAs),microRNAs(miRNAs),and circular RNAs(circRNAs).It can also be transcriptionally activated by the transcription factor adenovirus E2 factor 1(E2F1)and promote tumorigenesis and development through signaling pathways associated with tumorigenesis such as Wnt,phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt),rearrangement during transfection(RET)factor,murine double minute 2-p53(MDM2-p53),closely related to poor prognosis.With the deepening research on SPIN1,it has been found that SPIN1 may serve as a potential target for the treatment of various malignant tumors.Inhibitors targeting the interaction between SPIN1 and H3K4me3 have been developed to block the carcinogenic capacity of SPIN1.

关 键 词：SPIN1 组蛋白阅读器 恶性肿瘤 小分子抑制剂 

分 类 号：R730.2[医药卫生—肿瘤]