Abstract
BackgroundWilms’ tumor 1-associating protein (WTAP) is a nuclear protein, which is ubiquitously expressed in many tissues. Furthermore, in various types of malignancies WTAP is overexpressed and plays a role as an oncogene. The function of WTAP in diffuse large B-cell lymphoma (DLBCL), however, remains unclear.MethodsImmunohistochemistry was applied to evaluate the levels of WTAP expression in DLBCL tissues and normal lymphoid tissues. Overexpression and knock-down of WTAP in DLBCL cell lines, verified on mRNA and protein level served to analyze cell proliferation and apoptosis in DLBCL cell lines by flow cytometry. Finally, co-immunoprecipitation (Co-IP), IP, and GST-pull down assessed the interaction of WTAP with Heat shock protein 90 (Hsp90) and B-cell lymphoma 6 (BCL6) as well as determined the extend of its ubiquitinylation.ResultsWTAP protein levels were consistently upregulated in DLBCL tissues. WTAP promoted DLBCL cell proliferation and improved the ability to confront apoptosis, while knockdown of WTAP in DLBCL cell lines allowed a significant higher apoptosis rate after treatment with Etoposide, an anti-tumor drug. The stable expression of WTAP was depended on Hsp90. In line, we demonstrated that WTAP could form a complex with BCL6 via Hsp90 in vivo and in vitro.ConclusionWTAP is highly expressed in DLBCL, promoting growth and anti-apoptosis in DLBCL cell lines. WTAP is a client protein of Hsp90 and can appear in a complex with BCL6 and Hsp90 in DLBCL. Down-regulation of WTAP could improve the chemotherapeutic treatments in DLBCL.
Highlights
Wilms’ tumor 1-associating protein (WTAP) is a nuclear protein, which is ubiquitously expressed in many tissues
Client proteins are drawn into a multi-protein complex by Heat shock protein 90 (Hsp90), a molecular chaperone assisting in folding and stabilization of proteins [9]
WTAP was overexpressed in diffuse large B-cell lymphoma (DLBCL) To determine the expression status of WTAP in DLBCLs, we performed immunohistochemistry staining using DLBCL patients’ tissues (n = 30) (Additional file 1: Table S1) and normal lymphoid tissues (n = 30)
Summary
Wilms’ tumor 1-associating protein (WTAP) is a nuclear protein, which is ubiquitously expressed in many tissues. In various types of malignancies WTAP is overexpressed and plays a role as an oncogene. The function of WTAP in diffuse large B-cell lymphoma (DLBCL), remains unclear. Wilms’ tumor 1-associating protein (WTAP) is a nuclear protein first identified as a binding protein of Wilms’ tumor 1 (WT1) both in vitro and in vivo [1]. The biological function of WTAP in normal cells has been. WTAP is a novel oncogene in acute myelogenous leukemia (AML) and a client protein of Heat shock protein 90 (Hsp90) [8]. Client proteins are drawn into a multi-protein complex by Hsp, a molecular chaperone assisting in folding and stabilization of proteins [9]. Hsp is a rational therapeutic target for cancer [11]
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