Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2019; 11(8): 622-633
Published online Aug 15, 2019. doi: 10.4251/wjgo.v11.i8.622
shRNA-interfering LSD1 inhibits proliferation and invasion of gastric cancer cells via VEGF-C/PI3K/AKT signaling pathway
Hong-Ming Pan, Wei-Ya Lang, Li-Jie Yao, Yan Wang, Xiao-Ling Li
Hong-Ming Pan, Department of Biochemistry, Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
Wei-Ya Lang, Department of Histology and Embryology, Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
Li-Jie Yao, Yan Wang, Xiao-Ling Li, Department of Anatomy, Qiqihar Medical University, Qiqihar 161000, Heilongjiang Province, China
Author contributions: Pan HM, Lang WY, Yao LJ and Wang Y designed this work, collected and interpreted the data, and drafted the manuscript; Li XL designed this work, critically revised the manuscript, and performed overall supervision; all authors contributed to the final approval and accountability for the manuscript.
Supported by Doctoral Special Research Fund of Qiqihar Medical College, No. QY2016B-06.
Institutional review board statement: This study was reviewed and approved by the Qiqihar Medical University.
Conflict-of-interest statement: No conflict of interest exists.
Data sharing statement: No additional data are available.
Open-Access: 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. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Xiao-Ling Li, PhD, Associate Professor, Department of Anatomy, Qiqihar Medical University, No. 333 Bukui North Street, Jianhua District, Qiqihar 161006, Heilongjiang Province, China. lixiaoling0420@126.com
Telephone: +886-452-2663121
Received: May 16, 2019
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
Processing time: 91 Days and 22.4 Hours
ARTICLE HIGHLIGHTS
Research background

Epigenetics means that the DNA sequence is unchanged, and the cell phenotype or gene expression is genetically altered, mainly including DNA methylation, histone covalent modification, and chromatin remodeling. Among them, histone covalent modification activates or inhibits gene expression by regulating chromatin structure. 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. At present, there are few reports on the role of LSD1 expression level in the proliferation and metastasis of gastric cancer cells, and there is no literature reports on the role of VEGF-C/PI3K/AKT signaling pathway in LSD1 expression and the metastatic potential of gastric cancer. This research is innovative and can provide a theoretical basis for early diagnosis and targeted therapy of gastric cancer.

Research motivation

The main content of this study was to down-regulate the expression of LSD1 to observe the changes in the proliferation and invasion of human gastric cancer MKN-45 cells, and the role of VEGF-C/PI3K/AKT signaling pathway in inhibiting the metastasis of gastric cancer cells by down-regulating the expression of LSD1. Key questions to be addressed in this study: (1) The changes on the proliferation and invasion of human gastric cancer MKN-45 cells after down-regulating the expression of LSD1; and (2) The role of the VEGF-C/PI3K/AKT signaling pathway in it. Research significance: The results of this study will provide a new experimental basis for the early diagnosis and treatment of gastric cancer and the development of new targets for anti-tumor drugs, and add a new experimental basis for the study of epigenetics in cancer therapy.

Research objectives

The main goal was to investigate the down-regulation of the expression of LSD1 on the proliferation and invasion of human gastric cancer MKN-45 cell line and its mechanism. It has been found that down-regulation of LSD1 expression inhibits VEGF-C/PI3K/AKT signaling pathway and thereby inhibits gastric cancer cell metastasis. The results of this study will provide a new experimental basis for the early diagnosis and treatment of clinical gastric cancer and the development of new targets for anti-tumor drugs.

Research methods

In this study, human gastric cancer MKN-45 cell line was selected and transiently transfected with LSD1 shRNA interference plasmid to down-regulate the expression of LSD1. The proliferation and invasion ability of human gastric cancer MKN-45 cell line were observed by CCK-8 cell proliferation assay and Transwell invasion assay. Western Blot was used to detect changes in molecular protein levels associated with gastric cancer metastasis in the VEGF-C/PI3K/AKT signaling pathway.

Research results

This study found that down-regulation of LSD1 expression inhibits VEGF-C/PI3K/AKT signaling pathway and further inhibits gastric cancer cell metastasis. No relevant literature reports have been reported. In order to further study the effect of down-regulating LSD1 expression on lymphangiogenesis during gastric cancer cell metastasis, we need to study the effect of down-regulating LSD1 expression on the growth, migration and lumen formation of gastric cancer cell lymphatic endothelial cells in the future, and thus supplement the results of this study.

Research conclusions

Down-regulation of LSD1 expression inhibits the proliferation and invasion of human gastric cancer MKN-45 cell line. Down-regulation of LSD1 expression can inhibit VEGF-C/PI3K/AKT signaling pathway, which may be one of the important mechanisms for its inhibition of gastric cancer cell metastasis. Down-regulation of LSD1 expression can inhibit the proliferation and invasion of human gastric cancer MKN-45 cell line; down-regulation of LSD1 expression inhibits VEGF-C/PI3K/AKT signaling pathway, thereby inhibiting gastric cancer cell metastasis. Is down-regulation of LSD1 expression promoting or inhibiting the proliferation and invasion of human gastric cancer MKN-45 cell line. Down-regulation of LSD1 expression inhibits VEGF-C/PI3K/AKT signaling pathway and inhibits gastric cancer cell metastasis. Down-regulation of LSD1 expression inhibits VEGF-C/PI3K/AKT signaling pathway and thereby inhibits gastric cancer cell metastasis. Down-regulation of LSD1 expression can inhibit the proliferation and invasion of human gastric cancer MKN-45 cell line, and also can inhibit the metastasis of gastric cancer cells by restraining VEGF-C/PI3K/AKT signal pathway. Epigenetic research is important for the early diagnosis and treatment of tumors.

Research perspectives

This study has produced innovative results through common basic cell experiments. In this study, we intend to study the effect of down-regulating the expression of LSD1 on the growth, migration and lumen formation of lymphatic endothelial cells in gastric cancer cells, and to study the effect of down-regulating the expression of LSD1 on lymphangiogenesis during gastric cancer cell metastasis in order to supplement the results of this study. Animal experiments will also be performed to verify and supplement the results.