SEPTIN2 and STATHMIN Regulate CD99-Mediated Cellular Differentiation in Hodgkin's Lymphoma.
SEPTIN2 and STATHMIN Regulate CD99-Mediated Cellular Differentiation in Hodgkin's Lymphoma.
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DOI：
10.1371/journal.pone.0127568
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zhao T
中科院分区：
文献类型：
--
作者：
Jian W;Zhong L;Wen J;Tang Y;Qiu B;Wu Z;Yan J;Zhou X;Zhao T
霍奇金淋巴瘤（HL）是一种淋巴样肿瘤，其特征为霍奇金和里德-斯滕伯格（H/RS）细胞，受CD 99调节。我们先前报道了CD 99下调导致小鼠B淋巴瘤细胞（A20）转化为具有H/RS表型的细胞，而CD 99上调诱导经典霍奇金淋巴瘤（cHL）细胞（L428）分化为末端B细胞。然而，其分子机制仍不清楚。本研究采用荧光双向凝胶电泳和基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）技术，分析了L428细胞中CD 99上调和A20细胞中小鼠CD 99抗原样2（mCD 99 L2）下调后蛋白表达的变化。生物信息学分析表明，细胞骨架蛋白SEPTIN 2和STATHMIN的差异表达，并选择进一步验证和功能分析。在两种模型中均发现SEPTIN 2的差异表达，并与CD 99表达呈负相关。在A20细胞系模型中鉴定了STATHMIN，其表达与CD 99的表达正相关。重要的是，用SiRNA沉默SEPTIN 2大大改变了L428细胞的细胞骨架。通过siRNA下调STATHMIN促进H/RS细胞向终末B细胞分化。这些结果表明，SEPTIN 2介导的细胞骨架重排和STATHMIN介导的分化可能有助于细胞形态学的变化和H/RS细胞的分化与HL中的CD 99上调。
Hodgkin’s lymphoma (HL) is a lymphoid neoplasm characterized by Hodgkin’s and Reed-Sternberg (H/RS) cells, which is regulated by CD99. We previously reported that CD99 downregulation led to the transformation of murine B lymphoma cells (A20) into cells with an H/RS phenotype, while CD99 upregulation induced differentiation of classical Hodgkin’s lymphoma (cHL) cells (L428) into terminal B-cells. However, the molecular mechanism remains unclear. In this study, using fluorescence two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS), we have analyzed the alteration of protein expression following CD99 upregulation in L428 cells as well as downregulation of mouse CD99 antigen-like 2 (mCD99L2) in A20 cells. Bioinformatics analysis showed that SEPTIN2 and STATHMIN, which are cytoskeleton proteins, were significantly differentially expressed, and chosen for further validation and functional analysis. Differential expression of SEPTIN2 was found in both models and was inversely correlated with CD99 expression. STATHMIN was identified in the A20 cell line model and its expression was positively correlated with that of CD99. Importantly, silencing of SEPTIN2 with siRNA substantially altered the cellular cytoskeleton in L428 cells. The downregulation of STATHMIN by siRNA promoted the differentiation of H/RS cells toward terminal B-cells. These results suggest that SEPTIN2-mediated cytoskeletal rearrangement and STATHMIN-mediated differentiation may contribute to changes in cell morphology and differentiation of H/RS cells with CD99 upregulation in HL.
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