摘要
Argonaute(Ago)家族蛋白与小的非编码RNAs(siRNAs,miRNAs,piRNAs)生物发生和细胞功能密切相关.它可以结合小RNAs,调控蛋白质的合成或影响mRNA的稳定性,即RNA干扰(RNAi),并且参与Piwi相关RNAs(piRNAs)的生成.人类Argonaute蛋白家族包括8个成员,对其中的4个(Ago1～Ago4)mRNAs进行了实时定量PCR(qRT-PCR)检测,其在许多细胞中共表达,与细胞生长紧密相关.针对人乳腺癌MCF7和子宫颈癌HeLa细胞系,通过下调Ago亚族蛋白表达量,研究其在细胞周期中的调控作用.MTT实验证明,Ago蛋白表达缺失导致细胞增殖活性显著下降(P<0.01),生长受阻.进一步研究揭示,细胞周期在G0/G1期发生停滞,其中Ago1(P<0.01)和Ago4(P<0.05)的作用尤为明显,但并不引发凋亡.虽然具体调控机制尚不清晰,但在人类肿瘤细胞中Argonaute蛋白可直接或间接地参与细胞周期进程的调控.
Argonaute family piRNAs）. With their functional proteins are closely linked to small domains, Argonaute proteins can bind non-coding RNAs （siRNAs, microRNAs, small non-coding RNAs and control protein synthesis, finally affecting mRNA stability, namely RNA interference （RNAi）. Moreover, they also participate in the production of Piwi-interacting RNAs （piRNAs）. There are 8 members in the human Argonaute family. Using quantitative RT-PCR （qRT-PCR）, the expression levels of 4 Ago genes （Ago1-Ago4） were assayed. Experimental results indicated that these genes were ubiquitously expressed in many cell lines. Then it was investigated whether Argonaute subfamily proteins could influence cell cycle regulation by knocking down their expressions in human breast adenocarcinoma MCF-7 cells and cervical carcinoma HeLa cells. The lack of Ago expression resulted in decreased cellular proliferation activity. Further investigation revealed that the cell cycle was delayed at the G0/G1 phases with the especially remarkable arrest occurring in the cases of Ago1 （P 〈 0.01） and Ago4 （P 〈 0.05）, but without apoptosis. It suggests that Argonaute proteins may function in the cell cycle progression through a possible pathway that does not require small RNAs. The mechanisms underlying this phenomenon are still a puzzle for us.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2008年第12期1394-1402,共9页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金资助项目(30671042)~~
