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shRNA-interfering LSD1 inhibits proliferation and invasion of gastric cancer cells via VEGF-C/PI3K/AKT signaling pathway

BACKGROUND: 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 an...

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Autores principales: Pan, Hong-Ming, Lang, Wei-Ya, Yao, Li-Jie, Wang, Yan, Li, Xiao-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700030/
https://www.ncbi.nlm.nih.gov/pubmed/31435463
http://dx.doi.org/10.4251/wjgo.v11.i8.622
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author Pan, Hong-Ming
Lang, Wei-Ya
Yao, Li-Jie
Wang, Yan
Li, Xiao-Ling
author_facet Pan, Hong-Ming
Lang, Wei-Ya
Yao, Li-Jie
Wang, Yan
Li, Xiao-Ling
author_sort Pan, Hong-Ming
collection PubMed
description BACKGROUND: 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. AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
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spelling pubmed-67000302019-08-21 shRNA-interfering LSD1 inhibits proliferation and invasion of gastric cancer cells via VEGF-C/PI3K/AKT signaling pathway Pan, Hong-Ming Lang, Wei-Ya Yao, Li-Jie Wang, Yan Li, Xiao-Ling World J Gastrointest Oncol Basic Study BACKGROUND: 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. AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. Baishideng Publishing Group Inc 2019-08-15 2019-08-15 /pmc/articles/PMC6700030/ /pubmed/31435463 http://dx.doi.org/10.4251/wjgo.v11.i8.622 Text en ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Basic Study
Pan, Hong-Ming
Lang, Wei-Ya
Yao, Li-Jie
Wang, Yan
Li, Xiao-Ling
shRNA-interfering LSD1 inhibits proliferation and invasion of gastric cancer cells via VEGF-C/PI3K/AKT signaling pathway
title shRNA-interfering LSD1 inhibits proliferation and invasion of gastric cancer cells via VEGF-C/PI3K/AKT signaling pathway
title_full shRNA-interfering LSD1 inhibits proliferation and invasion of gastric cancer cells via VEGF-C/PI3K/AKT signaling pathway
title_fullStr shRNA-interfering LSD1 inhibits proliferation and invasion of gastric cancer cells via VEGF-C/PI3K/AKT signaling pathway
title_full_unstemmed shRNA-interfering LSD1 inhibits proliferation and invasion of gastric cancer cells via VEGF-C/PI3K/AKT signaling pathway
title_short shRNA-interfering LSD1 inhibits proliferation and invasion of gastric cancer cells via VEGF-C/PI3K/AKT signaling pathway
title_sort shrna-interfering lsd1 inhibits proliferation and invasion of gastric cancer cells via vegf-c/pi3k/akt signaling pathway
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700030/
https://www.ncbi.nlm.nih.gov/pubmed/31435463
http://dx.doi.org/10.4251/wjgo.v11.i8.622
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