Abstract
Quaking-5 (QKI-5) belongs to the STAR (signal transduction and activation of RNA) family of RNA binding proteins and functions as a tumor suppressor in several human malignancies. In this study, we attempt to elucidate the role of QKI-5 in the pro-metastasis processes of lung cancer (LC) cells and the underlying mechanisms. We confirmed that QKI-5 was decreased in human LC tissues and cell lines, especially in high-metastatic cells. Moreover, QKI expression was positively correlated with LC patients’ survival. Functional studies verified that QKI-5 suppressed migration, invasion and TGF-β1-induced epithelial-mesenchymal transition (EMT) of LC cells. Mechanistically, we affirmed that QKI-5 reduced β-catenin level in LC cells via suppressing its translation and promoting its degradation, whereas QKI-5 promoter hypermethylation suppressed QKI-5 expression. Our findings indicate that QKI-5 inhibits pro-metastasis processes of LC cells through interdicting β-catenin signaling pathway, and that QKI-5 promoter hypermethylation is a crucial epigenetic regulation reducing QKI-5 expression in LC cells, and reveal that QKI-5 is a potential prognostic biomarker for LC patients.
Highlights
Lung cancer (LC) currently ranks as one of the most prevalent neoplasms and the leading cause of cancer-related deaths worldwide [1]
We examined the expressions of QKI-5 mRNA and protein in two pairs of low and high metastatic lung cancer (LC) cell lines (AGZY vs ANIP, 95C vs 95D)
QKI-5 is a vital regulator of RNA processing and cell signal transduction, and the change of alternative mRNA splicing induced by its downexpression is an important cause accelerating cell proliferation in multiple cancers including LC [15,16,17]
Summary
Lung cancer (LC) currently ranks as one of the most prevalent neoplasms and the leading cause of cancer-related deaths worldwide [1]. Epithelial-mesenchymal transition (EMT) is a biological process that enables epithelial cells to acquire mesenchymal phenotype [6]. It can be triggered by various ligand-receptor interactions, including TGF-β1, and involves extensive regulatory networks which are www.impactjournals.com/oncotarget controlled by transcription factors and else [7]. Wnt/β-catenin signaling pathway is crucial in human malignancies, including LC [8]. Numerous studies have linked the metastasis and EMT induction with Wnt/β-catenin activation [9,10,11]. It is important to understand how the crosstalk between key factors and Wnt/βcatenin signaling pathway promotes the aggression of LC cells, which may provide new modalities for LC therapeutic intervention
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