Wilms 瘤 1 相关蛋白在弥漫性大 B 细胞淋巴瘤中发挥侵袭性作用，并通过热休克蛋白 90 与 BCL6 形成复合物。
Wilms' tumor 1-associating protein plays an aggressive role in diffuse large B-cell lymphoma and forms a complex with BCL6 via Hsp90.
机构信息
Department of Pathology and Pathophysiology, Institute of Pathology and Forensic Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Department of Medical Oncology, Institute of Clinical Science, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
出版信息
Cell Commun Signal. 2018 Aug 24;16(1):50. doi: 10.1186/s12964-018-0258-6.
BACKGROUND
Wilms' 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.
METHODS
Immunohistochemistry 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.
RESULTS
WTAP 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.
CONCLUSION
WTAP 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.
背景
Wilms 肿瘤 1 相关蛋白（WTAP）是一种核蛋白，在许多组织中广泛表达。此外，在各种类型的恶性肿瘤中，WTAP 过表达并发挥癌基因的作用。然而，WTAP 在弥漫性大 B 细胞淋巴瘤（DLBCL）中的功能尚不清楚。
方法
应用免疫组织化学方法评估 WTAP 在 DLBCL 组织和正常淋巴组织中的表达水平。通过流式细胞术分析 DLBCL 细胞系中 WTAP 的过表达和敲低对细胞增殖和凋亡的影响。最后，通过 co-immunoprecipitation（Co-IP）、IP 和 GST-pull down 评估 WTAP 与热休克蛋白 90（Hsp90）和 B 细胞淋巴瘤 6（BCL6）的相互作用以及其泛素化程度。
结果
WTAP 蛋白水平在 DLBCL 组织中持续上调。WTAP 促进 DLBCL 细胞增殖并提高细胞抗凋亡能力，而在 DLBCL 细胞系中敲低 WTAP 后，用抗肿瘤药物依托泊苷处理可显著提高细胞凋亡率。WTAP 的稳定表达依赖于 Hsp90。我们还证明了 WTAP 可以在体内和体外通过 Hsp90 与 BCL6 形成复合物。
结论
WTAP 在 DLBCL 中高表达，促进 DLBCL 细胞系的生长和抗凋亡。WTAP 是 Hsp90 的客户蛋白，可与 BCL6 和 Hsp90 形成复合物存在于 DLBCL 中。下调 WTAP 可改善 DLBCL 的化疗治疗效果。
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