PTBP3 mediates TGF-β-induced EMT and metastasis of lung adenocarcinoma

Lung adenocarcinoma (LUAD) is associated with a poor prognosis due to early metastasis to distant organs. TGF-beta potently induces epithelial-to-mesenchymal transition (EMT) and promotes invasion and metastasis of cancers. However, the mechanisms underlying this alteration are largely unknown. PTBP3 plays a critical role in RNA splicing and transcriptional regulation. Although accumulating evidence has revealed that PTBP3 exhibits a pro-oncogenic role in several cancers, whether and how PTBP3 mediates TGF-beta-induced EMT and metastasis in LUAD remains unknown. The expression levels and prognostic value of PTBP3 were analyzed in human LUAD tissues and matched normal tissues. siRNAs and lentivirus-mediated vectors were used to transfect LUAD cell lines. Various in vitro experiments including western blot, qRT-PCR, a luciferase reporter assay, chromatin immunoprecipitation (ChIP), transwell migration and invasion assay and in vivo metastasis experiment were performed to determine the roles of PTBP3 in TGF-beta-induced EMT and metastasis. PTBP3 expression was significantly upregulated in patients with LUAD, and high expression of PTBP3 indicated a poor prognosis. Intriguingly, we found that PTBP3 expression level in LUAD cell lines was significantly increased by exogenous TGF-beta 1 in a Smad-dependent manner. Mechanistically, p-Smad 3 was recruited to the PTBP3 promoter and activated its transcription. In turn, PTBP3 knockdown abolished TGF-beta 1-mediated EMT through the inhibition of Smad2/3 expression. Furthermore, PTBP3 overexpression increased lung and liver metastasis of LUAD cells in vivo. PTBP3 is indispensable to TGF-beta-induced EMT and metastasis of LUAD cells and is a novel potential therapeutic target for the treatment of LUAD.

Automated summary

The study revealed the critical role of PTBP3 in LUAD, with its high expression associated with poor prognosis. PTBP3 mediates TGF-beta-induced EMT and metastasis by activating the Smad pathway for transcription. This research provides a new potential therapeutic target for the treatment of LUAD.