PTBP3 mediates TGF-β-induced EMT and metastasis of lung adenocarcinoma.
PTBP3 mediates TGF-β-induced EMT and metastasis of lung adenocarcinoma.
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PTBP 3介导TGF-β诱导的肺腺癌EMT和转移
DOI：
10.1080/15384101.2022.2052530
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发表时间：
2022-07
期刊：
影响因子：
4.3
通讯作者：
Zhou, Yongxin
中科院分区：
文献类型：
--
作者：
Dong, Chenglai;Wu, Kaiqin;Gu, Shaorui;Wang, Wenli;Xie, Shiliang;Zhou, Yongxin
肺腺癌（LUAD）由于早期转移到远处器官而预后不良。TGF-β有效地诱导上皮向间质转化（EMT）并促进癌症的侵袭和转移。然而，这种改变的机制在很大程度上是未知的。PTBP 3在RNA剪接和转录调控中起关键作用。尽管越来越多的证据表明PTBP 3在几种癌症中表现出促癌作用，但PTBP 3是否以及如何介导LUAD中TGF-β诱导的EMT和转移仍不清楚。分析PTBP 3在LUAD组织和正常组织中的表达水平及其预后价值。使用siRNA和慢病毒介导的载体转染LUAD细胞系。进行各种体外实验，包括蛋白质印迹、qRT-PCR、荧光素酶报告基因测定、染色质免疫沉淀（ChIP）、transwell迁移和侵袭测定以及体内转移实验，以确定PTBP 3在TGF-β诱导的EMT和转移中的作用。PTBP 3在LUAD患者中表达显著上调，PTBP 3高表达提示预后不良。有趣的是，我们发现外源性TGF-β1以Smad依赖的方式显著增加LUAD细胞系中PTBP 3的表达水平。从机制上讲，p-Smad 3被募集到PTBP 3启动子并激活其转录。PTBP 3基因敲减可通过抑制Smad 2/3的表达而消除TGF-β1介导的EMT。此外，PTBP 3过表达增加LUAD细胞在体内的肺和肝转移。PTBP 3在TGF-β诱导的LUAD细胞EMT和转移过程中是不可或缺的，是治疗LUAD的一个新的潜在治疗靶点。
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.
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影响因子：
64.5
作者：
Mullen AC;Orlando DA;Newman JJ;Lovén J;Kumar RM;Bilodeau S;Reddy J;Guenther MG;DeKoter RP;Young RA
通讯作者：
Young RA
DOI：
10.1073/pnas.1407074111
发表时间：
2014-09-09
影响因子：
11.1
作者：
Risolino, Maurizio;Mandia, Nadia;Verde, Pasquale
通讯作者：
Verde, Pasquale
影响因子：
9
作者：
Liang X;Chen W;Shi H;Gu X;Li Y;Qi Y;Xu K;Zhao A;Liu J
通讯作者：
Liu J
人类无义介导的 RNA 衰变通过靶向肺腺癌中的 TGF-α 信号通路来调节 EMT
影响因子：
9.7
作者：
Cao, Lu;Qi, Lisha;Cao, Wenfeng
通讯作者：
Cao, Wenfeng
TGFβ 信号的背景
DOI：
10.1038/nrm3434
发表时间：
2012-10
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
通讯作者：
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