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PDGFBB facilitates tumorigenesis and malignancy of lung adenocarcinoma associated with PI3K-AKT/MAPK signaling

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机构： [1]Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China. [2]Institute of Neurological Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. [3]Laboratory Zoology Department, Institute of Neuroscience, Kunming Medical University, Kunming, China. [4]School of Integrated Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, China

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Lung adenocarcinoma (LUAD) remains one of the most aggressive tumors and the efficacy of conventional treatment has been bleak. Nowadays, gene-targeted therapy has become a new favorite in tumor therapy. Herein, we investigated the effect of platelet derived growth factor BB (PDGFBB) on LUAD. Firstly, PDGFBB was upregulated in LUAD patients and closely linked with poor survival. Furthermore, the expression of PDGFBB and PDGFRα/β in LUAD cells was higher than that in normal lung cells. By loss-of-function with herpes simplex virus (HSV)-PDGFi-shRNA, we found that PDGFBB knockdown caused a significant decrease in proliferation and migration, but evoked apoptosis of LUAD cells in vitro. Conversely, exogenous PDGFBB held adverse effect. Additionally, A549 cells with PDGFBB knockdown had a low probability of tumorigenesis in vivo. Moreover, PDGFBB knockdown restrained the growth of xenografts derived from normal A549 cells. Mechanistically, PDGFBB knockdown suppressed PI3K/AKT and Ras/MAPK signaling, while PDGFBB was the opposite. Therefore, we concluded that PDGFBB might facilitate the tumorigenesis and malignancy of LUAD through its functional downstream nodes-PI3K/AKT and Ras/MAPK signaling, which supported that PDGFBB could serve as a rational therapeutic target for LUAD.© 2024. The Author(s).

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大类 | 2 区综合性期刊

小类 | 2 区综合性期刊

第一作者：

第一作者机构： [1]Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China. [2]Institute of Neurological Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

通讯作者：

通讯机构： [1]Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China. [2]Institute of Neurological Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. [3]Laboratory Zoology Department, Institute of Neuroscience, Kunming Medical University, Kunming, China.

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