Abstract
WD-repeat protein 79 (WDR79), a member of the WD-repeat protein family, acts as a scaffold protein, participating in telomerase assembly, Cajal body formation and DNA double-strand break repair. Here, we first report that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung cancer (NSCLC). Knockdown of WDR79 significantly inhibited the proliferation of NSCLC cells in vitro and in vivo by inducing cell cycle arrest and apoptosis. WD-repeat protein 79 -induced cell cycle arrest at the G0/G1 phase was associated with the expression of G0/G1-related cyclins and cyclin-dependent kinase complexes. We also provide evidence that WDR79 knockdown induces apoptosis via a mitochondrial pathway. Collectively, these results suggest that WDR79 is involved in the tumorigenesis of NSCLC and is a potential novel diagnostic marker and therapeutic target for NSCLC.
Keywords:
apoptosis; cell cycle; lung cancer; proliferation.
© 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / genetics
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Carcinogenesis / genetics*
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Carcinogenesis / metabolism
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Carcinogenesis / pathology
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Carcinoma, Non-Small-Cell Lung / genetics*
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cell Line, Tumor
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Cyclins / genetics
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Cyclins / metabolism
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Disease Progression
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Female
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G1 Phase Cell Cycle Checkpoints / genetics
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Gene Expression Regulation, Neoplastic*
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Humans
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Intracellular Signaling Peptides and Proteins
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Lung Neoplasms / genetics*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Mice
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Mice, Nude
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Mitochondria / metabolism
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Molecular Chaperones
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Proteins / antagonists & inhibitors
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Proteins / genetics*
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Proteins / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Resting Phase, Cell Cycle / genetics
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Signal Transduction
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Telomerase
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Xenograft Model Antitumor Assays
Substances
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Carrier Proteins
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Cyclins
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ELP2 protein, human
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Intracellular Signaling Peptides and Proteins
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Molecular Chaperones
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Phosphoproteins
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Proteins
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RNA, Small Interfering
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Telomerase
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WRAP53 protein, human