Published online Aug 15, 2019. doi: 10.4251/wjgo.v11.i8.622
Peer-review started: May 21, 2019
First decision: July 22, 2019
Revised: July 31, 2019
Accepted: August 3, 2019
Article in press: August 3,2019
Published online: August 15, 2019
Histone Lysine Specific Demethylase 1 (LSD1) is the first histone demethylase to be discovered, which regulates various biological functions by making lysine of histone H3K4, H3K9 and non-histone substrates demethylated. Abnormal regulation of LSD1 is closely related to the occurrence and development of gastric cancer. The change of LSD1 expression level plays an important role in the proliferation and metastasis of gastric cancer cells. The study of its function and mechanism may provide a theoretical basis for early diagnosis and targeted therapy of gastric cancer.
To investigate the effect of downregulation of lysine-specific demethylase 1 (LSD1) expression on proliferation and invasion of gastric cancer cells and the possible regulatory mechanisms of the VEGF-C/PI3K/AKT signaling pathway.
The LSD1-specific short hairpin RNA (shRNA) interference plasmid was transiently transfected, and expression of LSD1 was downregulated. The cell proliferation ability of LSD1 was observed by CCK-8 assay after downregulating expression of LSD1. Transwell invasion assay was used to observe the change of cell invasion ability after downregulating expression of LSD1. Expression of phosphorylated phosphoinositide 3-kinase (p-PI3K), PI3K, p-AKT, AKT, vascular endothelial growth factor receptor (VEGFR)-3, matrix metalloproteinase (MMP)-2 and MMP-9 in each group was detected by Western blotting.
The cell proliferation ability of transiently transfected LSD1-shRNA interference plasmid group was significantly lower than that of the control group (P < 0.05). Transwell invasion assay showed that the number of cells across the membrane of the LSD1-shRNA transfection group (238.451 ± 5.216) was significantly lower than that of the control group (49.268 ± 6.984) (P < 0.01). Western blotting showed that expression level of VEGF-C, p-PI3K, PI3K, p-AKT, AKT, VEGFR-3, MMP-2 and MMP-9 in the LSD1-shRNA group was significantly lower than that in the control group (P < 0.05).
Downregulation of LSD1 expression inhibits metastatic potential of gastric cancer cells, and VEGF-C-mediated activation of PI3K/AKT signaling pathway, which may be an important mechanism for inhibiting lymph node metastasis in gastric cancer cells.
Core tip: The abnormal regulation of Lysine Specific Demethylase 1 (LSD1) is closely related to the occurrence and development of various cancers, such as gastric cancer. LSD1 is highly expressed in gastric cancer tissues, and the change in LSD1 expression level plays an important role in the proliferation and metastasis of gastric cancer cells. The VEGF-C/PI3K/AKT signaling pathway plays an important role in lymphangiogenesis and metastasis of gastric cancer. Therefore, this study investigated downregulation of LSD1 expression in order to observe the changes in gastric cancer cell proliferation and invasion, and further explored the role of the VEGF-C/PI3K/AKT signaling pathway. This study explores the role and mechanism of LSD1 in inhibiting gastric cancer cell metastasis from the perspective of epigenetics, providing a basis for early clinical diagnosis of gastric cancer metastasis.