title: SEPTIN2 and STATHMIN Regulate CD99-Mediated Cellular Differentiation in Hodgkin's Lymphoma.
abstract: 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.
authors.affiliation: Department of Molecular and Tumor Pathology Laboratory of Guangdong Province, School of Basic Medical Science, Southern Medical University, Guangzhou, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Jian
authors.affiliation: Department of Pathology, the Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of Molecular and Tumor Pathology Laboratory of Guangdong Province, School of Basic Medical Science, Southern Medical University, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Molecular and Tumor Pathology Laboratory of Guangdong Province, School of Basic Medical Science, Southern Medical University, Guangzhou, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Molecular and Tumor Pathology Laboratory of Guangdong Province, School of Basic Medical Science, Southern Medical University, Guangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qiu
authors.affiliation: Department of Molecular and Tumor Pathology Laboratory of Guangdong Province, School of Basic Medical Science, Southern Medical University, Guangzhou, China.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Molecular and Tumor Pathology Laboratory of Guangdong Province, School of Basic Medical Science, Southern Medical University, Guangzhou, China.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Molecular and Tumor Pathology Laboratory of Guangdong Province, School of Basic Medical Science, Southern Medical University, Guangzhou, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pathology, the Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
mesh_terms: D000071443:12E7 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000378:metabolism; D015536:Down-Regulation; D006689:Hodgkin Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D034741:RNA, Small Interfering; D058112:Septins / Q000235:genetics / Q000378:metabolism*; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D034741:RNA, Small Interfering; D050777:Stathmin; C000602252:SEPTIN2 protein, human; D058112:Septins