Knockdown of SSATX, an alternative splicing variant of the SAT1 gene, promotes melanoma progression

Gene. 2019 Oct 20:716:144010. doi: 10.1016/j.gene.2019.144010. Epub 2019 Jul 26.

Abstract

Alternative splicing can generate multiple protein messages from a single gene and has emerged as an important mechanism to regulate cancer pathways. The human SAT1 gene produces two transcript variants: one translates spermidine/spermine N-1 acetyltransferase (SSAT1), the rate-limiting enzyme in the catabolism of polyamines, and the other generates SSATX, which has largely unknown biological functions. Here, we used experimental data and analyses of several melanoma transcriptome datasets to reveal that SSATX is weakly expressed in melanoma cells. SSATX knockdown promoted the proliferation, migration, and invasion of human melanoma cells via the activation of the Wnt signaling pathway in a manner that was independent of SSAT1 expression. Based on our data, we propose that SSATX functions as a long non-coding RNA prior to its degradation in melanoma cells. Overall, our findings indicate that SSATX acts as a tumor suppressor, which may aid the future diagnosis and treatment of melanoma.

Keywords: Alternative splicing; Melanoma; SSATX; Tumor suppressor; Wnt signaling pathway.

MeSH terms

  • Acetyltransferases / genetics
  • Alternative Splicing
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Down-Regulation
  • Gene Knockdown Techniques
  • Humans
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Neoplasm Invasiveness
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / physiology*
  • Wnt Signaling Pathway

Substances

  • RNA, Long Noncoding
  • Acetyltransferases
  • diamine N-acetyltransferase