Long non-coding RNA SMASR inhibits the EMT by negatively regulating TGF-β/Smad signaling pathway in lung cancer

Oncogene. 2021 May;40(20):3578-3592. doi: 10.1038/s41388-021-01760-2. Epub 2021 Apr 30.

Abstract

TGF-β/Smad signaling pathway plays an important role in EMT during cancer progression. Long non-coding RNAs (lncRNAs) are involved in various behaviors of cancer cells, including EMT. Here, we report a novel lncRNA adjacent to Smad3, named Smad3-associated long non-coding RNA (SMASR). SMASR is downregulated by TGF-β via Smad2/3 in lung cancer cells. Knockdown of SMASR induces EMT and increases the migration and invasion of lung cancer cells. Moreover, knockdown of SMASR promotes the phosphorylation of Smad2/3. Mechanistically, SMASR interacts with Smad2/3 and inhibits the expression of TGFBR1, the TGF-β type I receptor responsible for phosphorylation of Smad2/3, thus leading to inactivation of TGF-β/Smad signaling pathway. Clinically, SMASR is downregulated in lung cancer tissues. Collectively, our findings prove a critical role of SMASR in EMT of lung cancer by forming a negative feedback loop with TGF-β/Smad signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / physiology
  • Epithelial-Mesenchymal Transition
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Phosphorylation
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Receptor, Transforming Growth Factor-beta Type I / genetics
  • Receptor, Transforming Growth Factor-beta Type I / metabolism*
  • Signal Transduction
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*

Substances

  • RNA, Long Noncoding
  • SMAD3 protein, human
  • Smad3 Protein
  • Transforming Growth Factor beta
  • Receptor, Transforming Growth Factor-beta Type I
  • TGFBR1 protein, human