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.

中文翻译：

---

SNHG5通过抵消STAU1介导的mRNA不稳定来促进结直肠癌细胞的存活。

我们目前对长非编码RNA（lncRNA）参与正常细胞过程和病理的了解有限。在这里，我们确定和表征SNHG5为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凋亡，并在体内限制肿瘤的生长，而SNHG5的过表达抵消了奥沙利铂诱导的凋亡。使用无偏的方法，我们确定与细胞质中的SNHG5相互作用的121个转录物位点。重要的是，敲低关键的SNHG5靶转录本，包括SPATS2，会诱导细胞凋亡，因此模拟了SNHG5耗尽后所见的作用。从机理上讲，我们建议SNHG5通过阻止STAU1降解目标转录物来稳定它们。因此，耗尽STAU1可以挽救SNHG5敲低后诱导的凋亡。因此，我们将SNHG5表征为在结肠直肠癌中促进肿瘤细胞存活的lncRNA，并描述了一种新的机制，其中细胞质lncRNA通过阻止STAU1的作用发挥功能。