PCAF-mediated acetylation of Lin28B increases let-7 biogenesis in lung adenocarcinoma H1299 cells.
PCAF-mediated acetylation of Lin28B increases let-7 biogenesis in lung adenocarcinoma H1299 cells.
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PCAF 介导的 Lin28B 乙酰化增加肺腺癌细胞 H1299 中 let-7 的生物合成
DOI：
10.1186/s12885-017-3959-0
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发表时间：
2018-01-04
期刊：
影响因子：
3.8
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Qu TT;Chen F;Wang J;Zhang YJ;Cheng MB;Sun WZ;Shen YF;Zhang Y
背景Lin 28 B及其副产物Lin 28 A是小RNA结合蛋白，具有相似的抑制作用，尽管它们靶向哺乳动物细胞中let-7 miRNAs成熟的不同步骤。由于Lin 28 B主要通过阻断let-7肿瘤抑制因子家族成员参与肿瘤的促进和发展，我们试图探索相关机制，以深入了解如何在人类癌细胞中降低Lin 28 B以增加let-7水平并逆转恶性肿瘤。直接与肺腺癌衍生的H1299细胞中的Lin 28 B相互作用并随后使其乙酰化。RT-qPCR分析显示，let-7a-1和let-7 g在PCAF转染的H1299细胞中均增加。结论乙酰化Lin 28 B对let-7a-1和let-7 g的影响与稳定敲低Lin 28 B对H1299细胞的影响相似。PCAF在H1299细胞中介导Lin 28 B乙酰化及其靶向microRNA的特异性释放中的新作用可能为let-7在肺癌患者临床治疗中的潜在应用提供线索。
BackgroundLin28B and its paralog Lin28A are small RNA binding proteins that have similar inhibitory effects, although they target separate steps in the maturation of let-7 miRNAs in mammalian cells. Because Lin28B participates in the promotion and development of tumors mostly by blocking the let-7 tumor suppressor family members, we sought to explore the associated mechanisms to gain insights into how Lin28B might be decreased in human cancer cells to increase let-7 levels and reverse malignancy.ResultsWe demonstrated that the histone acetyltransferase PCAF, via its cold shock domain, directly interacts with and subsequently acetylates Lin28B in lung adenocarcinoma-derived H1299 cells. RT-qPCR assays showed that both let-7a-1 and let-7g were increased in PCAF-transfected H1299 cells. Lin28B is acetylated by ectopic PCAF and translocates from the nucleus to the cytoplasm in H1299 cells.ConclusionsThe effects of acetylated Lin28B on let-7a-1 and let-7g are similar to that of stable knockdown of Lin28B in H1299 cells. The new role of PCAF in mediating Lin28B acetylation and the specific release of its target microRNAs in H1299 cells may shed light on the potential application of let-7 in the clinical treatment of lung cancer patients.
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影响因子：
64.5
作者：
Kugel S;Sebastián C;Fitamant J;Ross KN;Saha SK;Jain E;Gladden A;Arora KS;Kato Y;Rivera MN;Ramaswamy S;Sadreyev RI;Goren A;Deshpande V;Bardeesy N;Mostoslavsky R
通讯作者：
Mostoslavsky R
影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
PCAF 和 SIRT1 介导的 Lin28 可逆乙酰化
DOI：
10.1016/j.bbamcr.2014.03.001
发表时间：
2014-06-01
影响因子：
5.1
作者：
Wang, Ling-xia;Wang, Jing;Shen, Yu-fei
通讯作者：
Shen, Yu-fei
影响因子：
--
作者：
Yin J;Kim TH;Park N;Shin D;Choi HI;Cho S;Park JB;Kim JH
通讯作者：
Kim JH
影响因子：
64.8
作者：
Reinhart, BJ;Slack, FJ;Ruvkun, G
通讯作者：
Ruvkun, G