V-set and transmembrane domain-containing 1 is silenced in human hematopoietic malignancy cell lines with promoter methylation and has inhibitory effects on cell growth
V-set and transmembrane domain-containing 1 is silenced in human hematopoietic malignancy cell lines with promoter methylation and has inhibitory effects on cell growth
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V-set和含跨膜结构域1在具有启动子甲基化的人造血恶性肿瘤细胞系中被沉默，并对细胞生长具有抑制作用
DOI：
10.3892/mmr.2014.2785
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发表时间：
2015-02-01
影响因子：
3.4
通讯作者：
Han, Wenling
中科院分区：
文献类型：
--
作者：
Li, Ting;Guo, Xiaohuan;Han, Wenling
许多白细胞分化抗原作为造血系统恶性肿瘤研究、诊断、分诊和最终治疗靶点的重要标志物。VSTM 1是一个潜在的白细胞分化抗原基因。VSTM 1位于人类染色体上的19q13.4，这是一个重要的基因组区域，在许多造血系统恶性肿瘤中易于发生遗传和表观遗传修饰。VSTM 1-v1是由VSTM 1编码的一种主要剪接形式，是一种I型跨膜分子，具有细胞外免疫球蛋白V样结构域和两个细胞质免疫受体酪氨酸抑制基序。在本研究中，VSTM 1的表达在正常人外周血白细胞和造血肿瘤细胞系进行了检查，此外，VSTM 1基因的异常甲基化进行了评估，使用甲基化特异性聚合酶链反应（MSP）。本研究的结果表明，VSTM 1在正常人外周血白细胞中广泛表达，包括粒细胞和单核细胞，与以前的研究一致，以及淋巴细胞;此外，VSTM 1的分子大小和表达水平在白细胞之间有很大差异。然而，VSTM 1是检测不到的许多造血肿瘤细胞系启动子高甲基化。使用MSP和biosulfate基因组测序分析了VSTM 1基因和启动子区域的药理学诱导的去甲基化的影响，结果显示VSTM 1表达在甲基化沉默的Jurkat细胞中恢复。此外，CKK-8分析显示，VSTM 1-v1在Jurkat细胞中的过表达导致生长抑制。此外，在抗体诱导的VSTM 1-v1交联后，对细胞生长的抑制作用增强。总之，本研究的结果表明，启动子甲基化沉默VSTM 1和负调控人类造血系统恶性肿瘤细胞系的细胞生长。
Numerous leukocyte differentiation antigens act as important markers for research, diagnosis, triage and eventually treatment targets for hematopoietic malignancies. V-set and transmembrane domain-containing 1 (VSTM1) was identified by immunogenomic analysis as a potential leukocyte differentiation antigen gene. VSTM1 is located at 19q13.4 on human chromosomes, an important genomic region prone to genetic and epigenetic modifications in numerous hematopoietic malignancies. VSTM1-v1, a primary splicing form encoded by VSTM1, is a type I transmembrane molecule with an extracellular immunoglobulin V-like domain and two cytoplasmic immunoreceptor tyrosine-based inhibitory motifs. In the present study, VSTM1 expression was examined in normal human peripheral leukocytes and hematopoietic tumor cell lines; in addition, the aberrant methylation of the VSTM1 gene was evaluated using methylation-specific polymerase chain reaction (MSP). The results of the present study demonstrated that VSTM1 was widely expressed in normal human peripheral blood leukocytes, including granulocytes and monocytes, in concurrence with previous studies, as well as lymphocytes; in addition, the molecular size and expression levels of VSTM1 varied considerably between leukocytes. However, VSTM1 was undetectable in numerous hematopoietic tumor cell lines following promoter hypermethylation. The effects of pharmacologically-induced demethylation of the VSTM1 gene and promoter region were analyzed using MSP and biosulfite genomic sequencing, and the results revealed that VSTM1 expression was restored in methylation-silenced Jurkat cells. In addition, CKK-8 assays revealed that VSTM1-v1 overexpression in Jurkat cells resulted in growth suppression. Furthermore, the inhibitory effect on cell growth was enhanced following antibody-induced cross-linking of VSTM1-v1. In conclusion, the results of the present study indicated that promoter methylation silenced VSTM1 and negatively regulated cell growth in human hematopoietic malignancy cell lines.