In leukemia, knock-down of the death inducer-obliterator gene would inhibit the proliferation of endothelial cells by inhibiting the expression of CDK6 and CCND1

• Published in: PeerJ (San Francisco, CA) Vol. 10; p. e12832
• Main Authors: Cao, Honghua, Wang, Lilan, Geng, Chengkui, Yang, Man, Mao, Wenwen, Yang, Linlin, Ma, Yin, He, Ming, Zhou, Yeying, Liu, Lianqing, Hu, Xuejiao, Yu, Jingxing, Shen, Xiufen, Gu, Xuezhong, Yin, Liefen, Shen, Zhenglei
• Format: Journal Article
• Language: English
• Published: United States PeerJ. Ltd 01.02.2022; PeerJ, Inc; PeerJ Inc
• Subjects: Analysis; Angiogenesis; Antibodies; Apoptosis; Biochemistry; Bone marrow; Cancer; CCND1; CDK6; Cell Biology; Cell proliferation; Cell Proliferation - genetics; Chemotherapy; Cloning; Cyclin D1; Cyclin D1 - genetics; Cyclin-dependent kinase 6; Cyclin-Dependent Kinase 6 - genetics; DIDO; DNA probes; DNA-directed RNA polymerase; Endothelial cells; Endothelium; Enzymes; Extracellular signal-regulated kinase; Flow cytometry; Gene expression; Genes; Genetic aspects; Genetics; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Leukemia; Mitosis; Molecular Biology; Polymerase chain reaction; Proteins; RNA-mediated interference; Signal transduction; Umbilical vein; United States > US; DIDO; CDK6; CCND1; Leukemia; Endothelial cells
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.12832

Endothelial cells (ECs) are a critical component of the hematopoietic niche, and the cross-talk between ECs and leukemia was reported recently. This study aimed to determine the genes involved in the proliferation inhibition of endothelial cells in leukemia. Human umbilical vein endothelial cells (HUVEC) were cultured alone or co-cultured with K562 cell lines. GeneChip assays were performed to identify the differentially expressed genes. The Celigo, MTT assay, and flow cytometric analysis were used to determine the effect of RNAi DIDO on cell growth and apoptosis. The differently expressed genes were verified by qRT-PCR (quantitative real-time PCR) and western-blot. In K562-HUVEC co-cultured cell lines, 323 down-regulated probes were identified and the extracellular signal-regulated kinase 5 (ERK5) signaling pathway was significantly inhibited. Among the down-regulated genes, the ( ) is a part of the centrosome protein and may be involved in cell mitosis. As shown in the public data, leukemia patients with lower expression of showed a better overall survival (OS). The HUVEC cells were infected with lentivirus, and reduced expression, inhibited proliferation, and increased apoptosis was observed in cells. In addition, the expression of ( ) and ( ) genes was inhibited in cells. Finally, the public ChIP-seq data were used to analyze the regulators that bind with , and the H3K4me3 and PolII (RNA polymerase II) signals were found near the Exon1 and exon2 sites of . The knock-down of will inhibit the proliferation of endothelial cells in the leukemia environment. The expression of may be regulated by H3K4me3 and the inhibition of may lead to the down-regulation of and . However, how interacts with and requires further study.