Long non-coding RNA LINC00222 regulates GSK3β activity and promotes cell apoptosis in lung adenocarcinoma

Biomed Pharmacother. 2018 Oct:106:755-762. doi: 10.1016/j.biopha.2018.06.165. Epub 2018 Jul 11.

Abstract

Recent evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the regulating cellular processes such as differentiation, proliferation, metastasis and apoptosis. These lncRNAs are found to be dysregulated in a variety of cancers. However, the underlying mechanisms of lncRNAs action in lung adenocarcinoma remain unclear. We investigated expression of the lncRNA LINC00222 in 76 lung adenocarcinoma tissues and paired normal lung tissues and found that LINC00222 is downregulated in lung adenocarcinoma tissues. Enforced expression of LINC00222 significantly inhibited the proliferation, migration and invasive ability of lung adenocarcinoma cells, and also induced apoptosis. Furthermore, overexpression of LINC00222 enhanced the activity of glycogen synthase kinase-3β (GSK3β), which is a key element of the Wnt signaling pathway. Taken together, our findings suggest that LINC00222 acts as a tumor suppressor in lung adenocarcinoma and, therefore, could serve as a valuable prognostic biomarker and therapeutic target for lung adenocarcinoma patients.

Keywords: GSK3β; LINC00222; Lung cancer; Wnt signaling pathway.

MeSH terms

  • Adenocarcinoma of Lung / enzymology*
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / mortality
  • Adenocarcinoma of Lung / pathology
  • Aged
  • Apoptosis*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Proportional Hazards Models
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Time Factors

Substances

  • RNA, Long Noncoding
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta