title: TGF-β regulates the proliferation of lung adenocarcinoma cells by inhibiting PIK3R3 expression.
abstract: PIK3R3, an isoform of class IA phosphoinositide 3-kinase (PI3K), specifically interacts with cell proliferation regulators, such as retinoblastoma and proliferation cell nuclear antigen, to promote cell proliferation. However, the mechanisms behind the upstream signaling pathway of PIK3R3 remain unclear to date. This study showed that PIK3R3 expression was regulated by transforming growth factor-β (TGF-β) signaling and that PIK3R3 mediated the TGF-β-induced inhibition of lung adenocarcinoma cell proliferation. TGF-β down-regulated PIK3R3 expression in lung adenocarcinoma cells. However, this TGF-β-induced inhibition of cell proliferation can be attenuated by PIK3R3 overexpression. In addition, TGF-β can attenuate the transcriptional activity of NKX2.1, a transcription factor that binds to the promoter of PIK3R3. This result indicated that TGF-β regulated PIK3R3 expression by targeting NKX2.1. We confirmed the correlation between NKX2.1 and PIK3R3 in clinical samples. Therefore, the TGF-β/NKX2.1/PIK3R3 axis is crucial in the TGF-β-induced inhibition of cell proliferation, and the NKX2.1/PIK3R3 axis might become a target in TGF-β receptor-repressed lung adenocarcinoma.
authors.affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Guihua
authors.initials: G
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Thoracic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xuelai
authors.initials: X
authors.lastname: Luo
authors.affiliation: Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of immunology, School of Basic Medicine, Tongji Medical college, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D009687:Nuclear Proteins / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D017931:DNA Primers; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D019869:Phosphatidylinositol 3-Kinases; C523442:PIK3R3 protein, human
keywords: PIK3R3; TGF-β; cell proliferation; lung adenocarcinoma