Cell Death and Disease (Sep 2022)

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

  • Wei Xu,
  • Linna Chen,
  • Jiheng Liu,
  • Zhezhe Zhang,
  • Ranran Wang,
  • Qianqian Zhang,
  • Huiting Li,
  • Juanjuan Xiang,
  • Li Fang,
  • Ping Xu,
  • Zheng Li

DOI
https://doi.org/10.1038/s41419-022-05164-2
Journal volume & issue
Vol. 13, no. 9
pp. 1 – 13

Abstract

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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.