DNA损伤应答与细胞老化及癌变机制研究进展  

Research progress in the mechanisms of DNA damage response in cell senescence and carcinogenesis

作　　者：何路平 宁雪莲[1] 孙悦[1] 胡建东[1] 刘慧[2] 邱晓红[2] 周春水[1] 

机构地区：[1]哈尔滨医科大学基础医学院医学遗传学研究室,黑龙江哈尔滨150081 [2]哈尔滨医科大学附属第二医院妇产科,黑龙江哈尔滨150001

出　　处：《中华肿瘤防治杂志》2017年第11期783-787,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(81272582)

摘　　要：目的 DNA损伤是引起细胞老化的主要原因,细胞老化与肿瘤的发生发展密切相关。本研究旨在探讨DNA损伤应答和磷酸肌醇生物合成通路调控细胞老化及肿瘤发生的机制。方法以"肿瘤、DNA损伤、细胞老化和磷酸肌醇"等为关键词,检索PubMed、中国知网和万方数据库2000-01-2016-07的相关文献。纳入标准:(1)涉及到DNA损伤与细胞老化和肿瘤之间的相关性;(2)与磷酸肌醇生物合成通路对细胞老化和肿瘤的调控有关;(3)论述了细胞老化的相关表型及其产生机制。根据纳入标准,符合分析的文献42篇。结果 DNA损伤主要通过p53/p21、p16INK4a/pRB以及GATA4通路调控细胞老化进程。磷酸肌醇生物合成通路中的一些分子和蛋白激酶,如IP6、IP7和IP6K等也参与DNA损伤修复的调控,影响细胞老化及肿瘤发生。细胞老化既可以抑制肿瘤的发生也可以促进肿瘤的发生。结论DNA损伤应答和磷酸肌醇生物合成通路通过多种途径调控细胞老化及肿瘤的发生,为肿瘤的防治提供了新靶点。OBJECTIVE DNA damage is the main cause of cell senescence and tumorigenesis,which is closely related to carcinogenesis.This study aims to summarize the mechanisms of DNA damage response and inositol phosphate biosynthesis pathway in cell senescence and tumorigenesis.METHORDS We retrieved the papers published from January2000 to July 2016 with key words including tumor,DNA damage,senescence and inositol phosphate from PubMed,CNKI and Wanfang Data,42 papers were collected by the following criteria：（1）investigated the relationship between DNA damage and senescence or tumor.（2）related to the regulation of senescence and tumor through inositol phosphate biosynthesis.（3）discussed the senescent phenotypes and its causal mechanisms.RESULTS DNA damage mainly regulates senescence and tumor progression through p53/p21,p16INK4a/pRB,GATA4 signaling pathways.Molecules involved in inositol phosphate biosynthesis such as,IP6,IP7,IP6 K,also play roles in cell senescence and tumor progression.Cell senescence can not only inhibit but also promote the occurrence of tumor.CONCLUSIONS DNA damage response and inositol phosphate biosynthesis regulate senescence and tumor development through various mechanisms.These findings offer new drug targets for tumor prevention and treatment.

关 键 词：肿瘤发生 DNA损伤 磷酸肌醇 细胞老化 综述文献 

分 类 号：R730.2[医药卫生—肿瘤]