Integrated analysis of 10 lymphoma datasets identifies E2F8 as a key regulator in Burkitt's lymphoma and mantle cell lymphoma
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
Authors: Yang, An-Ping; Liu, Leyna G.; Chen, Min-Min; Liu, Fang; You, Hua; Liu, Lian; Yang, Hua; Xun, Yang; Liu, Jing; Wang, Rui-Xue; Brand, David D.; Liu, Dahai; Zheng, Song Guo; Li, Wen-Xing
Abstract
Burkitt's lymphoma (BURK), diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are three main types of B-cell lymphomas. This study aimed to compare the differences of affected biological functions and pathways, as well as to explore the possible regulatory mechanisms and the potential therapeutic targets in BURK, DLBCL and MCL. We performed an integrated analysis of 10 lymphoma datasets including 352 BURK patients, 880 DLBCL patients, 216 MCL patients, and 33 controls. Our results showed that signaling pathways, amino acid metabolism and several lipid metabolism pathways varies considerably among these three types of lymphoma. Furthermore, we identified several key transcription factors (TFs) and their target genes that may promote these diseases by influencing multiple carcinogenic pathways. Among these TFs, we reported first that E2F8 displayed the most significant effects in BURK and MCL. Our results demonstrate that over-expression of E2F8 activates target genes that may promote cell cycle, mitosis, immune and other cancer related functions in BURK and MCL. Therefore, we suggest that E2F8 could be used as a biomarker and potential therapeutic target for BURK and MCL. These findings would be helpful in the study of pathogenesis, and drug discovery and also in the prognosis of B cell lymphomas.
Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type
CANCERS
Authors: Priebe, Valdemar; Sartori, Giulio; Napoli, Sara; Chung, Elaine Yee Lin; Cascione, Luciano; Kwee, Ivo; Arribas, Alberto Jesus; Mensah, Afua Adjeiwaa; Rinaldi, Andrea; Ponzoni, Maurilio; Zucca, Emanuele; Rossi, Davide; Efremov, Dimitar; Lenz, Georg; Thome, Margot; Bertoni, Francesco
Abstract
Diffuse large B cell lymphoma (DLBCL) is a heterogenous disease that has been distinguished into at least two major molecular entities, the germinal center-like B cell (GCB) DLBCL and activated-like B cell (ABC) DLBCL, based on transcriptome expression profiling. A recurrent ch11q24.3 gain is observed in roughly a fourth of DLBCL cases resulting in the overexpression of two ETS transcription factor family members, ETS1 and FLI1. Here, we knocked down ETS1 expression by siRNA and analyzed expression changes integrating them with ChIP-seq data to identify genes directly regulated by ETS1. ETS1 silencing affected expression of genes involved in B cell signaling activation, B cell differentiation, cell cycle, and immune processes. Integration of RNA-Seq (RNA sequencing) data and ChIP-Seq (chromatin immunoprecipitation sequencing) identified 97 genes as bona fide, positively regulated direct targets of ETS1 in ABC-DLBCL. Among these was the Fc receptor for IgM, FCMR (also known as FAIM3 or Toso), which showed higher expression in ABC- than GCB-DLBCL clinical specimens. These findings show that ETS1 is contributing to the lymphomagenesis in a subset of DLBCL and identifies FCMR as a novel target of ETS1, predominantly expressed in ABC-DLBCL.