SNHG5 inhibits the progression of EMT through the ubiquitin-degradation of MTA2 in oesophageal cancer

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 S (SNHGS), a known lncRNA, is dysregulated in gastric cancer (GC). In this study, we explored the expression and function of SNHGS in development of ESCC. SNHGS 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 SNHGS significantly inhibited the proliferation, migration and invasion of ESCC cells in vivo and in vitro. Notably, we found that metastasis-associated protein 2 (MTA2) was pulled down by SNHGS in ESCC cells using RNA pulldown assay. We also found that SNHGS reversed the epithelial-mesenchymal transition by interacting with MTA2. In addition, overexpression of SNHGS downregulated the transcription of MTA2 and caused its ubiquitin-mediated degradation. Thus, overexpression of MTA2 partially abrogated the effect of SNHGS 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.

Automated summary

The downregulation of SNHGS is associated with cancer progression, clinical outcomes, and survival rates of ESCC patients. Overexpression of SNHGS significantly inhibits the proliferation, migration, and invasion of ESCC cells. SNHGS reverses the epithelial-mesenchymal transition by interacting with MTA2.