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

TGF-β 诱导的 LINC00152 通过 HuR 促进肺腺癌转移

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

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.

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