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

Lung adenocarcinoma (LUAD) is one of the main causes of cancer-related mortality, with a strong tendency to metastasize early. Transforming growth factor-beta (TGF-beta) signaling is a powerful regulator to promote metastasis of LUAD. Here, we screened long non-coding RNAs (lncRNAs) responsive to TGF-beta and highly expressed in LUAD cells, and finally obtained our master molecular LINC00152. We proved that the TGF-beta promoted transcription of LINC00152 through the classical TGF-beta/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-beta promotes metastasis depending HuR in lung adenocarcinoma. Designing targeting LINC00152 and HuR inhibitors may therefore be an effective therapeutic strategy for LUAD treatment.

Automated summary

This study reveals that TGF-beta-induced LINC00152 promotes metastasis in lung adenocarcinoma through the involvement of HuR and the regulation of transcription factors ZEB1, SNAI1, and SNAI2, which ultimately leads to epithelial-mesenchymal transition and enhanced metastatic ability.