Long non-coding RNA SNHG15 interacts with and stabilizes transcription factor Slug and promotes colon cancer progression

• Published in: Cancer letters Vol. 425; pp. 78 - 87
• Main Authors: Jiang, Hao, Li, Tingting, Qu, Yi, Wang, Xiang, Li, Bing, Song, Jiagui, Sun, Xiaoran, Tang, Yan, Wan, Junhu, Yu, Yu, Zhan, Jun, Zhang, Hongquan
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01-07-2018; Elsevier Limited
• Subjects: Cell fate; Cell migration; Colon cancer; Colorectal cancer; Cyclin-dependent kinases; DNA methylation; Ectopic expression; EMT; Gastric cancer; Gene expression; Genomes; Kinases; LncRNA; Medical prognosis; Metastases; Metastasis; Non-coding RNA; Nucleoli; Phosphorylation; Proteasomes; Proteins; Slug; SNHG15; snoRNA; Ubiquitin; Ubiquitination; Xenografts; Zinc; Zinc finger proteins; Beijing China; China; LncRNA; SNHG15; Colon cancer; Slug; EMT
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2018.03.038

Slug is a fast-turnover transcription factor critical for controlling cell fate and cancer cell invasion and metastasis. The stability of Slug is important and maintained by diverse mechanisms. In this study, we presented a paradigm of this activity by identifying long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) that binds to and stabilizes Slug in colon cancer cells. LncRNA SNHG15 transcription is upregulated in a variety of human cancers according to The Cancer Genome Atlas. Here, ectopic expression of SNHG15 promoted colon cancer cell migration in vitro, accelerated xenografted tumor growth in vivo, and elevated levels of SNHG15 were associated with poor prognosis for colon cancer patients. Mechanistically, SNHG15 maintains Slug stability in living cells by impeding its ubiquitination and degradation through interaction with the zinc finger domain of Slug. These findings revealed a novel mechanism underlying the control of Slug stability by demonstrating that oncogenic lncRNA SNHG15 interacts with and blocks Slug degradation via the ubiquitin-proteasome system.
•Long non-coding RNA (lncRNA) SNHG15 binds to the C-terminal zinc finger domain of Slug.•LncRNA SNHG15 stabilizes Slug by impeding Slug ubiquitination and degradation.•LncRNA SNHG15 promotes colon cancer cell migration and tumor growth in mice.•Elevated lncRNA SNHG15 expression predicts a poor prognosis for colon cancer patients.