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Lysine-specific demethylase 2 contributes to the proliferation of small cell lung cancer by regulating the expression of TFPI-2
The present study aimed to investigate the effect of lysine-specific demethylase 2 (LSD2) in small cell lung cancer (SCLC) and explore its underlying regulatory mechanism. Cell growth was tested by MTT assay and mRNA and protein expression was determined by quantitative polymerase chain reaction (q-...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059701/ https://www.ncbi.nlm.nih.gov/pubmed/29845195 http://dx.doi.org/10.3892/mmr.2018.9047 |
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author | Cao, Yunfeng Guo, Chunhui Yin, Yanhai Li, Xin Zhou, Ling |
author_facet | Cao, Yunfeng Guo, Chunhui Yin, Yanhai Li, Xin Zhou, Ling |
author_sort | Cao, Yunfeng |
collection | PubMed |
description | The present study aimed to investigate the effect of lysine-specific demethylase 2 (LSD2) in small cell lung cancer (SCLC) and explore its underlying regulatory mechanism. Cell growth was tested by MTT assay and mRNA and protein expression was determined by quantitative polymerase chain reaction (q-PCR) and western blot analysis, respectively. Chromatin immunoprecipitation (ChIP) was used to investigate the degree of H3K4me2 enrichment in the promoter region of tissue factor pathway inhibitor-2 (TFPI-2). SCLC tissues and cell lines presented significantly higher expression of LSD2 and DNA methyltransferase 3B (DNMT3B) and lower expression of TFPI-2 compared with the controls. In H1417 cells LSD2 overexpression increased the mRNA and protein expression of DNMT3B, while inhibiting the mRNA and protein expression of TFPI-2. Following transfection with short interfering (si) RNA-DNMT3B, the expression of TFPI-2 increased in H1417 cells. The results of ChIP demonstrated that compared with the controls, H3K4me1 enrichment in the TFPI-2 promoter region was to a lower degree in the H1417 cells with LSD2 overexpression and a higher degree in the H1417 cells with LSD2 silencing. MTT assays revealed that LSD2 overexpression significantly promoted the growth of H69, DMS-114 and H1417 cells, which was contradictory to the effect on LSD2 silencing. Compared with the LSD2 overexpression cells, SCLC cells with simultaneous overexpression of LSD2 and TFPI-2 demonstrated a decreased proliferation. These results suggest that LSD2 achieves a promoting effect on SCLC by indirectly regulating TFPI-2 expression through the mediation of DNMT3B expression or through the regulation of the demethylation of H3K4me1 in the promoter region of the TFPI-2 gene. |
format | Online Article Text |
id | pubmed-6059701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-60597012018-07-26 Lysine-specific demethylase 2 contributes to the proliferation of small cell lung cancer by regulating the expression of TFPI-2 Cao, Yunfeng Guo, Chunhui Yin, Yanhai Li, Xin Zhou, Ling Mol Med Rep Articles The present study aimed to investigate the effect of lysine-specific demethylase 2 (LSD2) in small cell lung cancer (SCLC) and explore its underlying regulatory mechanism. Cell growth was tested by MTT assay and mRNA and protein expression was determined by quantitative polymerase chain reaction (q-PCR) and western blot analysis, respectively. Chromatin immunoprecipitation (ChIP) was used to investigate the degree of H3K4me2 enrichment in the promoter region of tissue factor pathway inhibitor-2 (TFPI-2). SCLC tissues and cell lines presented significantly higher expression of LSD2 and DNA methyltransferase 3B (DNMT3B) and lower expression of TFPI-2 compared with the controls. In H1417 cells LSD2 overexpression increased the mRNA and protein expression of DNMT3B, while inhibiting the mRNA and protein expression of TFPI-2. Following transfection with short interfering (si) RNA-DNMT3B, the expression of TFPI-2 increased in H1417 cells. The results of ChIP demonstrated that compared with the controls, H3K4me1 enrichment in the TFPI-2 promoter region was to a lower degree in the H1417 cells with LSD2 overexpression and a higher degree in the H1417 cells with LSD2 silencing. MTT assays revealed that LSD2 overexpression significantly promoted the growth of H69, DMS-114 and H1417 cells, which was contradictory to the effect on LSD2 silencing. Compared with the LSD2 overexpression cells, SCLC cells with simultaneous overexpression of LSD2 and TFPI-2 demonstrated a decreased proliferation. These results suggest that LSD2 achieves a promoting effect on SCLC by indirectly regulating TFPI-2 expression through the mediation of DNMT3B expression or through the regulation of the demethylation of H3K4me1 in the promoter region of the TFPI-2 gene. D.A. Spandidos 2018-07 2018-05-22 /pmc/articles/PMC6059701/ /pubmed/29845195 http://dx.doi.org/10.3892/mmr.2018.9047 Text en Copyright: © Cao et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Cao, Yunfeng Guo, Chunhui Yin, Yanhai Li, Xin Zhou, Ling Lysine-specific demethylase 2 contributes to the proliferation of small cell lung cancer by regulating the expression of TFPI-2 |
title | Lysine-specific demethylase 2 contributes to the proliferation of small cell lung cancer by regulating the expression of TFPI-2 |
title_full | Lysine-specific demethylase 2 contributes to the proliferation of small cell lung cancer by regulating the expression of TFPI-2 |
title_fullStr | Lysine-specific demethylase 2 contributes to the proliferation of small cell lung cancer by regulating the expression of TFPI-2 |
title_full_unstemmed | Lysine-specific demethylase 2 contributes to the proliferation of small cell lung cancer by regulating the expression of TFPI-2 |
title_short | Lysine-specific demethylase 2 contributes to the proliferation of small cell lung cancer by regulating the expression of TFPI-2 |
title_sort | lysine-specific demethylase 2 contributes to the proliferation of small cell lung cancer by regulating the expression of tfpi-2 |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059701/ https://www.ncbi.nlm.nih.gov/pubmed/29845195 http://dx.doi.org/10.3892/mmr.2018.9047 |
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