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24 May 2019 : Laboratory Research  

High Glucose Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in A20 Murine Diffuse Large B-Cell Lymphoma Cells Through Increased Expression of High Mobility Group AT-Hook 2 (HMGA2)

Ya Wang1BCEG, Jie Tan2AEG*, Hongyan Wu1CD, Cunjian Yi3AF

DOI: 10.12659/MSM.916195

Med Sci Monit 2019; 25:3860-3868

Abstract

BACKGROUND: Patients with type 2 diabetes mellitus have been reported to be at increased risk of developing non-Hodgkin’s lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is the most common type of high-grade NHL. This study aimed to investigate the effects of high glucose on cell migration, invasion and epithelial-mesenchymal transition (EMT), and the expression of high mobility group AT-hook 2 (HMGA2) in A20 murine DLBCL cells.

MATERIAL AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the expression of HMGA2 at the gene and protein level and EMT markers in the A20 murine DLBCL cell line. A transwell assay evaluated cell migration and invasion of A20 cells. Short-interfering RNA (siRNA) was used to knockdown HMGA2 expression.

RESULTS: High glucose levels upregulated the expression of HMGA2, induced phenotypic changes of EMT, and increased cell migration and invasion in A20 cells. Knockdown of HMGA2 by siRNA effectively inhibited EMT induced by high glucose in A20 cells by directly regulating the Wnt/β-catenin signaling pathway.

CONCLUSIONS: In the A20 murine DLBCL cell line, high glucose upregulated the expression of HMGA2 to induce EMT and promote cell migration and invasion through the Wnt/β-catenin signaling pathway.

Keywords: High Mobility Group Proteins, Hyperglycemia, Lymphoma, Large B-Cell, Diffuse, Diabetes Mellitus, Type 2, Glucose, HMGA2 Protein, Lymphoma, Non-Hodgkin, RNA, Small Interfering

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750