肿瘤组织PIWI/piRNA通路蛋白对转座子作用机制研究进展

Research progress on PIWI/piRNA pathway proteins inhibiting transposon in tumors

目的同PIWI蛋白结合的RNAs(piRNAs)是一类新发现的非编码小RNA,其可抑制转座子并维持基因组的稳定性。肿瘤组织中可以检测到PIWI和piRNAs的表达,两者表达水平的变化可提示预后。总结PIWI/piRNA下游通路蛋白EXD1和CG9754抑制转座子活化、激活转座子高甲基化与促进转录沉默的作用机制。方法采用PubMed和CNKI期刊全文数据库检索系统,检索2003-01-01-2016-11-30相关文献,以"肿瘤、PIWI、piRNA、通路蛋白、转座子和转录沉默"为关键词检索英文文献420条,中文文献100条。纳入标准:PIWI/piRNA的生物学作用与肿瘤的关系;PIWI/piRNA通路蛋白的作用机制;PIWI/piRNA通路蛋白与转座子和转录沉默的关系,根据纳入标准,符合分析的文献40篇。结果 piRNA是一类新发现的非编码小RNA,PIWI和piRNA的表达水平与肿瘤类型以及肿瘤分期密切相关。Exonuclease domain-containing 1(EXD1)是MIWI2piRNA生物源性基因TDRD12的组成部分。转座子对基因有调节作用。EXD1作为piRNA的通路蛋白,可以辅助piRNA抑制转座的发生。缺少EXD1会引起转座子的活化和反转录转座子的增多。CG9754是转座子抑制和转录沉默过程中重要的piRNA的通路蛋白。CG9754同RNA或DNA的结合可以引起有效的转录沉默。结论 PIWI和piRNA表达水平与肿瘤类型以及分期密切相关,PIWI/piRNA通路蛋白和转座子的关系或许可以解释肿瘤细胞侵袭和转移的能力。PIWI、piRNA、EXD1和CG9754能为靶向治疗提供更多可能性。

OBJECTIVE PIWI-interacting RNAs（piRNAs）are a class of novel non-coding small RNA,they repress transposons and maintain genome integrity.PIWI and piRNAs have been identified in tumor issues,changes in both expression levels can prompt prognosis.To review the function of PIWI/piRNA and their relationship with tumors,summary the function of EXD1 and CG9754as the PIWI/piRNA downstream pathway proteins,and discuss their mechanism of inhibiting transposon,activating methylation of transposon,and promoting transcriptional silencing.METHODS Searched PubMed and CNKI database retrieval systems with＂Tumor＂and＂PIWI＂and＂piRNA＂and ＂pathway proteins＂and ＂transposon＂and ＂transcriptional silencing＂as key words in recent 13years（2003-01-01-2016-11-30）.Forty papers were finally selected according to the inclusion criteria as follows：the biological function of PIWI/piRNA and their relationship with the cancer;the mechanism of the PIWI/piRNA pathway proteins;the relationship between the PIWI/piRNA pathway proteins and the transposon and transcriptional silencing.RESULTS piRNA is a type of novel non-coding small RNA.The expression of PIWI and piRNA has relationship with the type and stage of tumors.Exonuclease domain-containing 1（EXD1）is a partner of the MIWI2 piRNA biogenesis factor TDRD12.Transposon can regulate genes.As the pathway protein of piRNA,EXD1 can assist piRNA inhibiting transposon.Losing of EXD1 leads to activate of transposon and increase retrotransposon.CG9754 is an essential piRNA pathway protein in transposon inhibiting and transcriptional silencing.CG9754 binds with RNA or DNA elicits potent transcriptional silencing.CONCLUSIONS The expression of PIWI and piRNA is closely related to tumor type and stage.The relationship between PIWI/piRNA pathway proteins and transposon may explain the capacity of invasion and metastasis in tumor cells.PIWI,piRNA,EXD1,CG9754 may propose possibility for target treatment.