Back to Search
Start Over
Lysine‑specific demethylase 2 contributes to the proliferation of small cell lung cancer by regulating the expression of TFPI‑2
- Source :
- Molecular Medicine Reports
- Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Male
Cancer Research
Lung Neoplasms
Biochemistry
03 medical and health sciences
0302 clinical medicine
lysine-specific demethylase 2
Cell Line, Tumor
Genetics
Gene silencing
Humans
MTT assay
Molecular Biology
Cell Proliferation
Glycoproteins
Histone Demethylases
Cell growth
Chemistry
Transfection
Articles
Cell cycle
Middle Aged
Molecular biology
Small Cell Lung Carcinoma
Neoplasm Proteins
Gene Expression Regulation, Neoplastic
030104 developmental biology
Real-time polymerase chain reaction
Oncology
Cell culture
030220 oncology & carcinogenesis
Molecular Medicine
Female
small cell lung cancer
methylation
Chromatin immunoprecipitation
tissue factor pathway inhibitor-2
Subjects
Details
- ISSN :
- 17913004
- Volume :
- 18
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular medicine reports
- Accession number :
- edsair.doi.dedup.....f297bc857bc97f3fe44e4f8701406dbc