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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Decreased expression of the long non-coding RNA HOXD-AS2 promotes gastric cancer progression by targeting HOXD8 and activating PI3K/Akt signaling pathway
Lin Yao, Peng-Cheng Ye, Wang Tan, Ya-Jun Luo, Wan-Ping Xiang, Zi-Lin Liu, Zhi-Ming Fu, Fei Lu, Ling-Han Tang, Jiang-Wei Xiao
Lin Yao, Department of Gastrointestinal Surgery, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu 610000, Sichuan Province, China, The Hepatobiliary Research Institute, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Lin Yao, Peng-Cheng Ye, Zhi-Ming Fu, Fei Lu, Ling-Han Tang, Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, The Hepatobiliary Research Institute, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Wang Tan, Department of Gastrointestinal Surgery, Yaan People’s Hospital, Yaan 625000, Sichuan Province, China
Ya-Jun Luo, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
Wan-Ping Xiang, Department of Thoracic Surgery, Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China
Zi-Lin Liu, Jiang-Wei Xiao, Department of Gastrointestinal Surgery, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu 610000, Sichuan Province, China
Author contributions: Yao L and Xiao JW conceived and designed the experiments; Yao L and Ye PC did most of the experiments and data analysis; Yao L wrote the manuscript; Ye PC, Fu ZM, Lu F, and Tang LH collected the clinical samples; Tan W, Yao L, and Xiang WP performed data analysis; Xiao JW revised the manuscript; and all authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 30700773, No. 81070378, and No. 81270561; and Sichuan Outstanding Youth Fund Project, No. 2015JQ0060.
Institutional review board statement: All the gastric cancer tissue samples were collected with written informed consent in accordance with the Declaration of Helsinki and with the approval of The Ethical Committee of The Affiliated Hospital of North Sichuan Medical College.
Conflict-of-interest statement: The authors declare that they have no competing interests to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Jiang-Wei Xiao, MD, PhD, Postdoc, Professor, Surgeon, Surgical Oncologist, Teacher, Department of Gastrointestinal Surgery, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, No. 278 Baoguang Road, Xindu District, Chengdu 610000, Sichuan Province, China. xiaojiangwei2018@163.com
Received: July 24, 2020
Peer-review started: July 24, 2020
First decision: September 17, 2020
Revised: September 27, 2020
Accepted: October 21, 2020
Article in press: October 21, 2020
Published online: November 15, 2020
ARTICLE HIGHLIGHTS
Research background
Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs with a length of more than 200 nucleotides and lack an open reading frame. They mainly regulate RNA transcription and mRNA splicing and play an important role in regulating the stability of RNA in the cytoplasm and the activity of microRNAs. More and more studies have shown that abnormally expressed lncRNAs are involved in all aspects of tumor occurrence and development, and are closely related to tumor proliferation, apoptosis, invasion, metastasis, drug resistance, and poor prognosis. In recent years, more and more studies have found that abnormally expressed lncRNAs are involved in the occurrence and development of gastric cancer (GC), and they are expected to become new biomarkers for the diagnosis and treatment of GC.
Research motivation
GC is one of the most common malignant tumors in the world. The incidence and mortality of GC are in the forefront of all malignant tumors. Although a major breakthrough has been achieved in the study of lncRNAs in the pathogenesis of GC, the specific mechanism of lncRNAs in the occurrence and development of GC has not yet been fully elucidated. Exploring new lncRNAs can help to understand the molecular mechanism of GC more deeply.
Research objectives
The main purpose of this study was to explore the effect of downregulation of HOXD-AS2 on the biological behavior of GC cells SGC-7901 and SNU-1 and the underlying mechanism. Studies have found that the downregulation of HOXD-AS2 can regulate the expression of its neighboring gene HOXD8, and can also activate the PI3K/Akt signaling pathway, thereby promoting the progression of GC cells. The results of this study may provide a new idea for the treatment of GC.
Research methods
The pcHOXD-AS2 plasmid vector was constructed and transfected into SGC-7901 and SNU-1 GC cells. Matrigel Transwell and wound healing assays were used to confirm the effect of HOXD-AS2 on invasion and migration of GC cells. Cell counting kit-8 assay and flow cytometry were used to verify the effect of HOXD-AS2 on proliferation, cell cycle, and apoptosis of GC cells. The relevant regulatory mechanism between HOXD-AS2 and HOXD8 and PI3K/Akt signaling pathway was verified by Western blot analysis.
Research results
In this study, we found that the low expression of lncRNA HOXD-AS2 was associated with lymph node metastasis and tumor-node-metastasis stage in GC. In vitro functional experiments demonstrated that overexpression of HOXD-AS2 inhibited GC cell progression. Mechanistic studies revealed that HOXD-AS2 regulated the expression of its nearby gene HOXD8 and inhibited the activity of the PI3K/Akt signaling pathway.
Research conclusions
These results indicate that downregulation of HOXD-AS2 significantly promotes the progression of GC cells by regulating HOXD8 expression and activating the PI3K/Akt signaling pathway. HOXD-AS2 may be a novel diagnostic biomarker and effective therapeutic target for GC.
Research perspectives
This study combines basic experimental research and bioinformatics results to reach a relatively novel conclusion. To further confirm the results of this study, siRNA and animal experiments may be better.
