Metadherin contributes to the pathogenesis of diffuse large B-cell lymphoma.

Abstract

BACKGROUND:

Metadherin (MTDH) has been demonstrated as a potentially crucial mediator of various types of human malignancies. However, the expression and role of MTDH in diffuse large-B-cell lymphoma (DLBCL) have not been reported yet. This study aimed to illuminate the role of MTDH in the pathogenesis of DLBCL.

METHODOLOGY/PRINCIPAL FINDINGS:

A remarkable elevation of MTDH on mRNA level was detected in DLBCL tissues by quantitative polymerase chain reaction (PCR). Using Western-blot analysis we found that the expression of MTDH protein was significantly upregulated in DLBCL cell lines and DLBCL tissues compared with peripheral blood mononuclear cells (PBMCs) from healthy samples and tissues from patients of reactive hyperplasia of lymph node. The results showed high expression of MTDH in 23 of 30 (76.67%) DLBCL tissues by using immunohistochemical analysis and the over expression of MTDH was strongly correlated to the clinical staging of patients with DLBCL (P<0.05). Furthermore, the finding suggested that the increase of MTDH in DLBCL cells could distinctly enhance cell proliferation and inhibit cell apoptosis; meanwhile, inhibition of MTDH expression by specific siRNA clearly enhanced LY8 cell apoptosis. Upregulation of MTDH elevated the protein level of total β-catenin and translocation of β-catenin to the nucleus directly or indirectly. Knockdown of MTDH decreased the level of total, cytoplasmic β-catenin and reduced nuclear accumulation of β-catenin protein. This indicated that the function of MTDH on the development of DLBCL was mediated through regulation of Wnt/β-catenin signaling pathway.

CONCLUSIONS/SIGNIFICANCE:

Our results suggest that MTDH contributes to the pathogenesis of DLBCL mediated by activation of Wnt/β-catenin pathway. This novel study may contribute to further investigation on the useful biomarkers and potential therapeutic target in the DLBCL patients.

• Authors: Xueling Ge, Xiao Lv, Lili Feng, Xiaoqian Liu, Junming Gao, Na Chen, Xin Wang
• Journal: PloS one (PLoS One) Vol. 7 Issue 6 Pg. e39449 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22768080 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules
• MTDH protein, human
• Membrane Proteins
• RNA, Messenger
• RNA, Small Interfering
• RNA-Binding Proteins
• Tumor Necrosis Factor-alpha
• beta Catenin

Topics

• Aged
• Apoptosis (drug effects, genetics)
• Cell Adhesion Molecules (genetics, metabolism)
• Cell Line, Tumor
• Cell Nucleus (drug effects, metabolism)
• Cell Proliferation (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Knockdown Techniques
• Humans
• Immunohistochemistry
• Lymphoma, Large B-Cell, Diffuse (genetics, pathology)
• Male
• Membrane Proteins
• Middle Aged
• Protein Transport (drug effects)
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (metabolism)
• RNA-Binding Proteins
• Tumor Necrosis Factor-alpha (pharmacology)
• Up-Regulation (drug effects, genetics)
• Wnt Signaling Pathway (drug effects)
• beta Catenin (genetics, metabolism)