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RBBP4 promotes colon cancer malignant progression <i>via</i> regulating Wnt/β-catenin pathway

Yandong Li, Zhen Lv, Weifang Zhu

2020World Journal of Gastroenterology25 citationsDOIOpen Access PDF

Abstract

BACKGROUND: Our previous study demonstrated that RBBP4 was upregulated in colon cancer and correlated with poor prognosis of colon cancer and hepatic metastasis. However, the potential biological function of RBBP4 in colon cancer is still unknown. AIM: To investigate the biological role and the potential mechanisms of RBBP4 in colon cancer progression. METHODS: Real-time polymerase chain reaction and western blot analysis were used to detect the expression of RBBP4 in colon cancer cell lines. The cell proliferation and viability of SW620 and HCT116 cells with RBBP4 knockdown was detected by Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine staining. The transwell assay was used to detect the invasion and migration capabilities of colon cancer cells with RBBP4 knockdown. Flow cytometry apoptosis assay was used to detect the apoptosis of colon cancer cells. Western blotting analysis was used to detect the expression of epithelial-mesenchymal transition and apoptosis related markers in colon cancer. The nuclear translocation of β-catenin was examined by Western blotting analysis in colon cancer cells with RBBP4 knockdown. The TOPFlash luciferase assay was used to detect the effect of RBBP4 on Wnt/β-catenin activation. The rescue experiments were performed in colon cancer cells treated with Wnt/β-catenin activator LiCl and RBBP4 knockdown. RESULTS: regulating proteins related to epithelial-mesenchymal transition. Knockdown of RBBP4 significantly inhibited survivin-mediated apoptosis. Mechanistically, the TOPFlash assay showed that RBBP4 knockdown increased activity of the Wnt/β-catenin pathway. Meanwhile, RBBP4 knockdown suppressed nuclear translocation of β-catenin. With Wnt/β-catenin activator, rescue experiments suggested that the role of RBBP4 in colon cancer progression was dependent on Wnt/β-catenin pathway. CONCLUSION: increasing activity of the Wnt/β-catenin pathway. RBBP4 may serve as a novel therapeutic target in colon cancer.

Topics & Concepts

Gene knockdownCancer researchWnt signaling pathwayEpithelial–mesenchymal transitionColorectal cancerBiologyCell growthApoptosisCancerViability assayMetastasisSurvivinMolecular biologyFlow cytometrySignal transductionCell biologyBiochemistryGeneticsWnt/β-catenin signaling in development and cancerHeat shock proteins researchCancer Cells and Metastasis
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