PTBP3 mediates TGF-β-induced EMT and metastasis of lung adenocarcinoma. Issue 13 (3rd July 2022)

• Record Type: Journal Article
• Authors: Dong, Chenglai; Wu, Kaiqin; Gu, Shaorui; Wang, Wenli; Xie, Shiliang; Zhou, Yongxin
• Is Part Of: Cell cycle. Volume 21:Issue 13(2022)
• Page Start: 1406
• Page End: 1421
• Publication Date: 2022-07-03
• Subjects: LUAD -- PTBP3 -- TGF-β/Smad signaling -- EMT -- tumor metastasis; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2022.2052530
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: Lung adenocarcinoma (LUAD) is associated with a poor prognosis due to early metastasis to distant organs. TGF-β 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-β-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-β-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-β1 in a Smad-dependent manner. Mechanistically, p-Smad3 was recruited to the PTBP3 promoter and activated its transcription. In turn, PTBP3 knockdown abolished TGF-β1-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-β-induced EMT and metastasis of LUAD cells and is a novel potential therapeutic target for the treatment of LUAD.