SNHG5 inhibits the progression of EMT through the ubiquitin-degradation of MTA2 in oesophageal cancer
SNHG5 inhibits the progression of EMT through the ubiquitin-degradation of MTA2 in oesophageal cancer
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SNHG5 通过泛素降解食管癌中 MTA2 抑制 EMT 进展
DOI：
10.1093/carcin/bgaa110
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发表时间：
2021
期刊：
影响因子：
4.7
通讯作者：
Shan Baoen
中科院分区：
文献类型：
--
作者：
Wei Sisi;Sun Shiping;Zhou Xinliang;Zhang Cong;Li Xiaoya;Dai Suli;Wang Yaojie;Zhao Lianmei;Shan Baoen
大部分转录物被称为长链非编码RNA（lncRNA），这些转录物在癌症的发展中起着关键作用。然而，关于lncRNA在食管鳞状细胞癌（ESCC）中的功能及其相关机制的研究报道甚少。在我们以前的研究中，我们证明了小核仁RNA宿主基因5（SNHG 5），一种已知的lncRNA，在胃癌（GC）中失调。本研究旨在探讨SNHG 5在食管鳞癌发生发展中的作用。SNHG 5在人食管鳞癌组织和细胞系中表达下调，这种下调与食管鳞癌患者的癌症进展、临床结局和生存率相关。此外，我们还发现SNHG 5的过表达在体内和体外都能显著抑制食管鳞癌细胞的增殖、迁移和侵袭。值得注意的是，我们发现转移相关蛋白2（MTA 2）在ESCC细胞中被SNHG 5用RNA下拉分析拉低。我们还发现SNHG 5通过与MTA 2相互作用逆转上皮-间充质转化。此外，SNHG 5的过表达下调了MTA 2的转录，并导致其泛素介导的降解。因此，在ESCC细胞系中，MTA 2的过表达部分消除了SNHG 5的作用。此外，我们发现MTA 2 mRNA表达在ESCC标本中显著升高，SNHG 5和MTA 2表达之间呈负相关。总的来说，这项研究首次证明了SNHG 5调节的MTA 2在ESCC的进展中起着重要作用，并为ESCC提供了一种新的潜在治疗策略。
A substantial fraction of transcripts are known as long noncoding RNAs (lncRNAs), and these transcripts play pivotal roles in the development of cancer. However, little information has been published regarding the functions of lncRNAs in oesophageal squamous cell carcinoma (ESCC) and the underlying mechanisms. In our previous studies, we demonstrated that small nucleolar RNA host gene 5 (SNHG5), a known lncRNA, is dysregulated in gastric cancer (GC). In this study, we explored the expression and function of SNHG5 in development of ESCC. SNHG5 was found to be downregulated in human ESCC tissues and cell lines, and this downregulation was associated with cancer progression, clinical outcomes and survival rates of ESCC patients. Furthermore, we also found that overexpression of SNHG5 significantly inhibited the proliferation, migration and invasion of ESCC cellsin vivoandin vitro. Notably, we found that metastasis-associated protein 2 (MTA2) was pulled down by SNHG5 in ESCC cells using RNA pulldown assay. We also found that SNHG5 reversed the epithelial–mesenchymal transition by interacting with MTA2. In addition, overexpression of SNHG5 downregulated the transcription of MTA2 and caused its ubiquitin-mediated degradation. Thus, overexpression of MTA2 partially abrogated the effect of SNHG5 in ESCC cell lines. Furthermore, we found that MTA2 mRNA expression was significantly elevated in ESCC specimens, and a negative correlation between SNHG5 and MTA2 expression was detected. Overall, this study demonstrated, for the first time, that SNHG5-regulated MTA2 functions as an important player in the progression of ESCC and provide a new potential therapeutic strategy for ESCC.