Quaking-5 suppresses aggressiveness of lung cancer cells through inhibiting β-catenin signaling pathway
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Xuexia Zhou1, Xuebing Li2, Cuiyun Sun1, Cuijuan Shi1, Dan Hua1, Lin Yu3, Yanjun Wen1, Feng Hua4, Qian Wang1, Qinghua Zhou2 and Shizhu Yu1
1Department of Neuropathology, Tianjin Key Laboratory of Injuries, Variations and Regeneration of The Nervous System, Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System of Education Ministry, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China
2Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China
3Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences of Tianjin Medical University, Tianjin 300070, China
4Department of Surgery, Shandong Cancer Hospital and Institute, Jinan 250117, China
Shizhu Yu, email: [email protected]
Keywords: QKI-5, lung cancer, pro-metastasis processes, β-catenin, methylation
Received: November 10, 2016 Accepted: June 11, 2017 Published: July 07, 2017
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.
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