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

Li,Ting; Guo,Xiaohuan; Wang,Wenyan; Mo,Xiaoning; Wang,Pingzhang; Han,Wenling

doi:10.3892/mmr.2014.2785

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

Authors:
- Ting Li
- Xiaohuan Guo
- Wenyan Wang
- Xiaoning Mo
- Pingzhang Wang
- Wenling Han
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Affiliations: Peking University Center for Human Disease Genomics, Beijing 100191, P.R. China
Published online on: October 27, 2014 https://doi.org/10.3892/mmr.2014.2785
Pages: 1344-1351

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Abstract

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.

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