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Downregulation of BarH‐like homeobox 2 promotes cell proliferation, migration and aerobic glycolysis through Wnt/β‐catenin signaling, and predicts a poor prognosis in non‐small cell lung carcinoma

作者:Hao Chen, Maowei Zhang, Wenhui Zhang, Yuanqin Li, Jiechen Zhu, Xiaojiao Zhang, Li Zhao, Shuyang Zhu, Bi Chen · 发表于:Thoracic Cancer · 年份:2018 · DOI:10.1111/1759-7714.12593 · 被引用次数:26 · 研究领域:Wnt/β-catenin signaling in development and cancer、Developmental Biology and Gene Regulation、Connective tissue disorders research

BACKGROUND: Human BarH-like homeobox 2 (Barx2), a homeodomain factor of the Bar family, plays a critical role in cell adhesion and cytoskeleton remodeling, and has been reported in an increasing array of tumor types except non-small cell lung carcinoma (NSCLC). The purpose of the current study was to characterize the expression of Barx2 and assess the clinical significance of Barx2 in NSCLC. METHODS: Quantitative real-time polymerase chain reaction, immunohistochemistry and western blot analysis were used to examine mRNA and protein expression, respectively. The relationships between Barx2 expression and clinicopathological variables were analyzed. Cell Counting Kit-8 and plate colony formation assay were used to detect cell proliferation. Transwell assay was used to examine cell migration ability. Glucose uptake, lactate, adenosine triphosphate, and lactate dehydrogenase assays were used to detect aerobic glycolysis. RESULTS: Barx2 is downregulated in NSCLC tissues compared with para-carcinoma. Furthermore, Barx2 expression shows a negative correlation with advanced TNM stage and a high level of Ki-67. Survival analysis reveals that Barx2 level is an independent prognostic factor for NSCLC patients. The Barx2 (low) Ki-67 (high) group had the worst prognosis. Furthermore, the data indicate that downregulation of Barx2 expression promotes cell proliferation, migration, and aerobic glycolysis, including increased lactate dehydrogenase activity, glucose utilization, lactate prod...