机构：[1]Department of Cancer Biotherapy Center, Yunnan Cancer Hospital, The Third Affiliated Hospital, Kunming Medical University, Xishan, Kunming, Yunnan 650000, P.R. China.[2]Department of Radiotherapy Oncology, The First Affiliated Hospital of Kunming Medical University, First School of Clinical Medicine, Kunming Medical University, Xishan, Kunming, Yunnan 650000, P.R. China.昆明医科大学附属第一医院[3]Department of Pathology, Yunnan Cancer Hospital, The Third Affiliated Hospital, Kunming Medical University, Xishan, Kunming, Yunnan 650000, P.R. China.[4]Department of Medical Oncology, Yunnan Cancer Hospital, The Third Affiliated Hospital, Kunming Medical University, Xishan, Kunming, Yunnan 650000, P.R. China.
Protein phosphatase 1 (PP1) inhibitors play a role in tumor progression through different mechanisms. Protein phosphatase 1 regulatory subunit 14D (PPP1R14D) is an inhibitor of PP1. However, the role of PPP1R14D in tumors and its mechanism of action are largely unknown. The purpose of the present study was to investigate the expression, function and mechanism of PPP1R14D in lung adenocarcinoma (LUAD). In the present study, GEPIA database analysis and immunohistochemistry demonstrated that PPP1R14D was highly expressed in LUAD tissues and that the expression of PPP1R14D in LUAD was negatively correlated with the age of patients and positively correlated with the 8th American Joint Committee on Cancer staging among patients. In addition, Kaplan‑Meier Plotter database analysis showed that PPP1R14D expression was associated with lower survival rates in patients with LUAD. PPP1R14D knockdown significantly inhibited LUAD cell proliferation, migration and invasion and induced LUAD cell arrest at the G1 phase of the cell cycle. Mechanistic analyses revealed that PPP1R14D knockdown may inhibit cell proliferation, migration and invasion by inactivating PKCα/BRAF/MEK/ERK pathway signaling and its downstream key proteins c‑Myc/Cyclin E1‑CDK2 and MMP2/MMP9/Vimentin. Moreover, knockdown of PPP1R14D suppressed tumor growth in vivo. All these results showed that PPP1R14D plays an important role in LUAD tumorigenesis and may serve as a potential prognostic factor and therapeutic target in LUAD.
基金：
National Natural Science Foundation of China; Scientific Research Fund of Education Department of Yunnan Province [81660389, 81602029]; Joint Special Funds for the Department of Science and Technology of Yunnan Province-Kunming Medical University [2022J0212]; [202201AY070001-144]
第一作者机构：[1]Department of Cancer Biotherapy Center, Yunnan Cancer Hospital, The Third Affiliated Hospital, Kunming Medical University, Xishan, Kunming, Yunnan 650000, P.R. China.
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通讯作者：
推荐引用方式(GB/T 7714)：
Cao Huijun,Wang Zhiqiang,Wang Ying,et al.PPP1R14D promotes the proliferation, migration and invasion of lung adenocarcinoma via the PKCα/BRAF/MEK/ERK signaling pathway[J].INTERNATIONAL JOURNAL OF ONCOLOGY.2022,61(6):doi:10.3892/ijo.2022.5443.
APA：
Cao Huijun,Wang Zhiqiang,Wang Ying,Ye Lijuan,Li Ruilei...&Ge Chunlei.(2022).PPP1R14D promotes the proliferation, migration and invasion of lung adenocarcinoma via the PKCα/BRAF/MEK/ERK signaling pathway.INTERNATIONAL JOURNAL OF ONCOLOGY,61,(6)
MLA：
Cao Huijun,et al."PPP1R14D promotes the proliferation, migration and invasion of lung adenocarcinoma via the PKCα/BRAF/MEK/ERK signaling pathway".INTERNATIONAL JOURNAL OF ONCOLOGY 61..6(2022)
