Long noncoding RNAs AC026904.1 is essential for TGF-β-induced migration and epithelial-mesenchymal transition through functioning as an enhancer of Slug in lung cancer cells

Environ Toxicol. 2020 Sep;35(9):942-951. doi: 10.1002/tox.22930. Epub 2020 Apr 9.

Abstract

Long noncoding RNA (lncRNA) AC026904.1 has been confirmed to be necessary for breast cancer metastasis. This work aims to investigate the effects of lncRNA AC026904.1 on lung cancer metastasis. We found that lncRNA AC026904.1 displayed a higher level in metastatic lung cancer tissues than adjacent tissues and nonmetastatic lung cancer tissues, and lung cancer cells treated with TGF-β. The expression of AC026904.1 was increased by the non-canonical TGF-β signaling. Additionally, AC026904.1 acts as an enhancer of the key metastatic factor Slug in the nucleus. This AC026904.1/Slug axis is necessary for TGF-β-mediated migration and epithelial-mesenchymal transition in lung cancer cells. This work firstly uncovers that AC026904.1 increases Slug expression at transcriptional level and subsequently plays critical effects in lung cancer metastasis, providing novel evidences that AC026904.1 holds great potential to be used as a marker for metastatic lung cancer.

Keywords: AC026904.1; LncRNA; TGF-β; lung cancer; metastasis; slug.

MeSH terms

  • A549 Cells
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics*
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung / metabolism
  • Lung / pathology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Neoplasm Metastasis
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism*
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Up-Regulation

Substances

  • RNA, Long Noncoding
  • RNA, Small Interfering
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Transforming Growth Factor beta