Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5 2200 Copenhagen, Denmark.
Department for Molecular Medicine, Aarhus University Hospital, Brendstrupgaardsvej 21 8000 Aarhus, Denmark.
Nat Commun. 2016 Dec 22;7:13875. doi: 10.1038/ncomms13875.
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.
我们目前对长非编码 RNA（lncRNA）在正常细胞过程和病理中的参与了解有限。在这里，我们鉴定并表征了 SNHG5，它是一种在结直肠癌中表达上调的稳定细胞质 lncRNA。SNHG5 的耗竭在体外诱导细胞周期停滞和细胞凋亡，并限制体内肿瘤生长，而 SNHG5 的过表达则抵消奥沙利铂诱导的细胞凋亡。通过一种无偏的方法，我们鉴定了 121 个与细胞质中的 SNHG5 相互作用的转录本位点。重要的是，关键 SNHG5 靶转录本的敲低，包括 SPATS2，诱导细胞凋亡，从而模拟了 SNHG5 耗竭后观察到的效果。从机制上讲，我们认为 SNHG5 通过阻止 STAU1 降解靶转录本来稳定靶转录本。因此，STAU1 的耗竭挽救了 SNHG5 敲低后诱导的细胞凋亡。因此，我们将 SNHG5 表征为一种促进结直肠癌肿瘤细胞存活的 lncRNA，并描绘了一种新的机制，即细胞质 lncRNA 通过阻止 STAU1 的作用发挥功能。
