LINC00152 induced by TGF-β promotes metastasis via HuR in lung adenocarcinoma

Cell Death Dis. 2022 Sep 7;13(9):772. doi: 10.1038/s41419-022-05164-2.

Abstract

Lung adenocarcinoma (LUAD) is one of the main causes of cancer-related mortality, with a strong tendency to metastasize early. Transforming growth factor-β (TGF-β) signaling is a powerful regulator to promote metastasis of LUAD. Here, we screened long non-coding RNAs (lncRNAs) responsive to TGF-β and highly expressed in LUAD cells, and finally obtained our master molecular LINC00152. We proved that the TGF-β promoted transcription of LINC00152 through the classical TGF-β/SMAD3 signaling pathway and maintained its stability through the RNA-binding protein HuR. Moreover, LINC00152 increased ZEB1, SNAI1 and SNAI2 expression via increasing the interactions of HuR and these transcription factors, ultimately promoting epithelial-mesenchymal transition of LUAD cell and enhancing LUAD metastasis in vivo. These data provided evidence that LINC00152 induced by TGF-β promotes metastasis depending HuR in lung adenocarcinoma. Designing targeting LINC00152 and HuR inhibitors may therefore be an effective therapeutic strategy for LUAD treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung* / pathology
  • Cell Line, Tumor
  • ELAV-Like Protein 1* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / pathology
  • RNA, Long Noncoding* / genetics
  • Transforming Growth Factor beta* / pharmacology

Substances

  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • RNA, Long Noncoding
  • Transforming Growth Factor beta
  • long non-coding RNA Linc00152, human