title: Knockdown of EWSR1/FLI1 expression alters the transcriptome of Ewing sarcoma cells in vitro.
abstract: Ewing sarcoma breakpoint region 1 (EWSR1) fusion with Friend leukemia integration 1 transcription factor (FLI1) induced by a translocation of chromosome 11 with 22 contributes to Ewing sarcoma development. To date, the precise molecular mechanisms about EWSR1/FLI1 involving in Ewing sarcoma development remains to be defined. This study explored the potential critical gene targets of EWSR1/FLI1 knockdown in Ewing sarcoma cells on the gene expression profile based on online dataset, performed Limma algorithm for differentially expressed genes identification, constructed the transcriptional factor (TF)-gene regulatory network based on integrate transcriptional regulatory element database (TRED). The data showed up- and down-regulation of differentially expressed genes over time and peaked at 72 h after EWSR1/FLI1 knockdown in Ewing sarcoma cells. SMAD3 were up-regulated and FLI1, MYB, E2F1, ETS2, WT1 were down-regulated with more than half of their targets were down-regulated after EWSR1/FLI1 knockdown. The Gene Ontology (GO) and pathway annotation of these differentially expressed genes showed a consistent trend in each group of samples. Totally, there were 355 differentially expressed genes occurring in all five comparison groups of different time points, in which 39 genes constructed a dysregulated TF-gene network in Ewing sarcoma cell line A673 after EWSR1/FLI1 knockdown. These data demonstrated that knockdown of EWSR1/FLI1 expression led to transcriptome changes in Ewing sarcoma cells and that Ewing sarcoma development and progression caused by altered EWSR1/FLI1 expression may be associated with more complex transcriptome changes.
authors.affiliation: Clinical Laboratory of Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710054, China.
authors.forename: Jihan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Clinical Laboratory of Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710054, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Clinical Laboratory of Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710054, China.
authors.forename: Yuzhu
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Clinical Laboratory of Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710054, China.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Clinical Laboratory of Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710054, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Clinical Laboratory of Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710054, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Wang
authors.affiliation: Clinical Laboratory of Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710054, China.
authors.forename: Heping
authors.initials: H
authors.lastname: Zhao
keywords: Ewing sarcoma; Ewsr1/fli1 fusion protein; Transcriptional factors-gene regulatory network; Transcriptome