Author:
Zhu Liwen,Chen Chuqin,Kang Meiyun,Ma Xiaopeng,Sun Xiaoyan,Xue Yao,Fang Yongjun
Abstract
Abstract
Objective
To identify key gene in childhood acute lymphoblastic leukemia (ALL) through weighted gene co-expression network analysis (WGCNA), and their enriched biological functions and signaling pathways.
Methods
Array data of the GSE73578 dataset, involving 46 childhood ALL samples, were acquired from the Gene Expression Omnibus (GEO) database. Hub modules associated with childhood ALL were screened out by WGCNA. Enriched biological functions and signaling pathways were then identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Hub genes were selected by overlapping those between down-regulated genes in GSE73578, GSE4698 and the hub module. Guilt by association (GBA) was adopted to verify the function of the identified KIF11 gene and to predict its target genes. Regulatory effects of KIF11 on the proliferation and cell cycle progression of ALL in vitro were determined by cytological experiments.
Results
WGCNA showed that the yellow module was the most relevant to childhood ALL treatment, containing 698 genes that were enriched in cell division, mitotic nuclear division, DNA replication and DNA repair, cell cycle, DNA replication and the P53 signaling pathway. The KIF11 gene was screened out and predicted as a cell cycle mediator in childhood ALL. Knockdown of KIF11 in ALL cells inhibited cell proliferation and arrested cell cycle progression in G2/M phase.
Conclusions
The KIF11 gene is critical in the treatment process of childhood ALL, which is a promising therapeutic target for childhood ALL.
Funder
Nanjing Medical Science and Technology Development Project
National Natural Science Foundation of China
Young Talent Support Project of Children’s Hospital of Nanjing Medical University
Special Fund for Health Science and Technology Development in Nanjing
Scientific Research Projects of Jiangsu Health Commission
Natural Science Foundation of Jiangsu Province
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,General Medicine