SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization.
SNHG5 promotes colorectal cancer cell survival by counteracting STAU1-mediated mRNA destabilization.
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DOI：
10.1038/ncomms13875
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发表时间：
2016-12-22
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
目前，我们对长链非编码RNA（lncRNA）参与正常细胞过程和病理学的知识有限。在这里，我们确定和表征SNHG 5作为一个稳定的细胞质lncRNA与上调表达的结直肠癌。SNHG5的耗尽在体外诱导细胞周期停滞和凋亡，并限制体内肿瘤生长，而SNHG5过表达抵消奥沙利铂诱导的凋亡。使用无偏的方法，我们确定了121个转录位点与SNHG5在细胞质中的相互作用。重要的是，关键SNHG5靶转录物（包括SPATS 2）的敲低诱导细胞凋亡，从而模拟SNHG5耗尽后观察到的效果。从机制上讲，我们认为SNHG 5通过阻断STAU 1对靶转录物的降解来稳定靶转录物。因此，STAU 1的消耗挽救了SNHG 5敲低后诱导的细胞凋亡。因此，我们将SNHG 5描述为促进结直肠癌中肿瘤细胞存活的lncRNA，并描绘了一种新的机制，其中细胞质lncRNA通过阻断STAU 1的作用发挥作用。几种lncRNA与癌症有关。在这里，作者将SNHG 5鉴定为一种长的非编码RNA，通过保护特定的mRNA免受STAU 1介导的降解，促进结直肠癌细胞的增殖和存活。
We currently have limited knowledge of the involvement of long non-coding RNAs (lncRNAs) in normal cellular processes and pathologies. Here, we identify and characterize SNHG5 as a stable cytoplasmic lncRNA with up-regulated expression in colorectal cancer. Depletion of SNHG5 induces cell cycle arrest and apoptosis in vitro and limits tumour outgrowth in vivo, whereas SNHG5 overexpression counteracts oxaliplatin-induced apoptosis. Using an unbiased approach, we identify 121 transcript sites interacting with SNHG5 in the cytoplasm. Importantly, knockdown of key SNHG5 target transcripts, including SPATS2, induces apoptosis and thus mimics the effect seen following SNHG5 depletion. Mechanistically, we suggest that SNHG5 stabilizes the target transcripts by blocking their degradation by STAU1. Accordingly, depletion of STAU1 rescues the apoptosis induced after SNHG5 knockdown. Hence, we characterize SNHG5 as a lncRNA promoting tumour cell survival in colorectal cancer and delineate a novel mechanism in which a cytoplasmic lncRNA functions through blocking the action of STAU1. Several lncRNAs have been linked to cancer. Here, the authors identify SNHG5 as a long non-coding RNA promoting proliferation and survival of colorectal cancer cells by protecting specific mRNAs from STAU1-mediated degradation.
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影响因子：
5.9
作者：
Dong, Xue-Yuan;Guo, Peng;Boyd, Jeff;Sun, Xiaodong;Li, Qunna;Zhou, Wei;Dong, Jin-Tang
通讯作者：
Dong, Jin-Tang
影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
DOI：
10.1073/pnas.1006732107
发表时间：
2010-10-19
影响因子：
11.1
作者：
Liu, Huiping;Patel, Manishkumar R.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.