Lysine‑specific demethylase 2 contributes to the proliferation of small cell lung cancer by regulating the expression of TFPI‑2

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.

A Comparative Study of Biological Characteristics and Transcriptome Profiles of Mesenchymal Stem Cells from Different Canine Tissues

“…Among the up-regulated gene expression in body-derived MSCs, the TFPI2 gene has been identified as a tumor suppressor gene in several types of cancers [51]; DPT is a kind of extracellular matrix protein, which is considered to be the communication link between the surface and extracellular matrix environment of dermal fibroblasts. The control of TGF-beta bioavailability and the calibration of TGF-beta and BMP levels can adjust osteoblast maturation [52], which suggests that the high osteogenic differentiation efficiency of body-derived MSCs in previous studies may be connected with their own high expression.…”

Lysine-specific histone demethylase 1B (LSD2/KDM1B) represses p53 expression to promote proliferation and inhibit apoptosis in colorectal cancer through LSD2-mediated H3K4me2 demethylation

“…The common demethylases include histone demethylase containing the jumonji C (JmjC) domain [ 8 ] and FAD-dependent lysine-specific demethylase (LSDs), including LSD1 and LSD2 [ 9 – 11 ]. LSD2 plays important roles in gene silencing, transcription factor activity regulation, and cell cycle regulation in the occurrence and development of many types of tumors [ 10 , 12 – 14 ]. Moreover, LSD2 overexpression predicts aggressive tumor biology and poor prognosis [ 15 ].…”

Biomarker expression analysis in different age groups revealed age was a risk factor for breast cancer

“…As a Kunitz serine protease inhibitor, TFPI2 can inhibit many serine proteases, including trypsin, plasmin, plasma kallikrein, and chymotrypsin (Li et al, 2016). Studies have shown that the low expression of TFPI2 in small cell lung cancer (SCLC) can promote proliferation of the cells (Cao, Guo, Yin, Li, & Zhou, 2018). In addition, TFPI2 is closely related to apoptosis and angiogenesis in cervical cancer, and its expression tends to decrease with the progression of cancer (Zhang et al, 2012).…”