Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2024; 16(8): 3559-3584
Published online Aug 15, 2024. doi: 10.4251/wjgo.v16.i8.3559
Expression and significant roles of the long non-coding RNA CASC19/miR-491-5p/HMGA2 axis in the development of gastric cancer
Li-Xiang Zhang, Pan-Quan Luo, Zhi-Jian Wei, A-Man Xu, Tao Guo
Li-Xiang Zhang, Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei 230031, Anhui Province, China
Li-Xiang Zhang, Anhui Provincial Key Laboratory of Digestive Disease, Hefei 230031, Anhui Province, China
Pan-Quan Luo, Zhi-Jian Wei, A-Man Xu, Tao Guo, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230031, Anhui Province, China
Tao Guo, Anhui Public Health Clinical Center, Hefei 230000, Anhui Province, China
Co-first authors: Li-Xiang Zhang and Pan-Quan Luo.
Co-corresponding authors: Tao Guo and A-Man Xu.
Author contributions: Zhang LX write the main work; Luo PQ helped finish the experiments and write the manuscript; Xu AM designed this study; Wei ZJ and Guo T revised this manuscript; Zhang LX and Luo PQ contribute this work equally as co-first author; Xu AM and Guo T contribute this work equally as co-corresponding authors; all authors read and approved the final manuscript.
Supported by Natural Science Foundation of Anhui Province, No. 2108085QH337; Research Fund of Anhui Medical University, No. 2022xkj156; Key Projects of Anhui Provincial Department of Education, No. 2023AH053330; and Anhui Institute of Translational Medicine Research Fund, No. 2022zhyx-C88.
Institutional review board statement: This study was approved by Institutional Review Board of the First Affiliated Hospital of Anhui Medical University.
Institutional animal care and use committee statement: The studies involving animals were reviewed and approved by the Ethics Committee of the Anhui Medical University.
Conflict-of-interest statement: All authors declare no conflict of interest.
Data sharing statement: The data used to support the findings of this study are available from the corresponding author upon request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Tao Guo, PhD, Professor, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Shushan Street, Hefei 230031, Anhui Province, China. ahguotao@163.com
Received: December 20, 2023
Revised: April 25, 2024
Accepted: June 12, 2024
Published online: August 15, 2024
Processing time: 231 Days and 12.5 Hours
Abstract
BACKGROUND

Gastric cancer (GC) is a common malignant tumor, long non-coding RNA and microRNA (miRNA) are important regulators that affect tumor proliferation, metastasis and chemotherapy resistance, and thus participate in tumor progression. CASC19 is a new bio-marker which can promote tumor invasion and metastasis. However, the mechanism by which CASC19 affects the progression of GC through miRNA is not clear.

AIM

To explore the role of the CASC19/miR-491-5p/HMGA2 regulatory axis in GC.

METHODS

To explore the expression and prognosis of CASC19 in GC through clinical samples, and investigate the effects of inhibiting CASC19 on the proliferation, migration, invasion and other functions of GC cells through cell counting Kit-8 (CCK-8), ethynyldeoxyuridine, Wound healing assay, Transwell, Western blot and flow cytometry experiments. The effect of miR-491-5p and HMGA2 in GC were also proved. The regulatory relationship between CASC19 and miR-491-5p, miR-491-5p and HMGA2 were validated through Dual-luciferase reporter gene assay and reverse transcription PCR. Then CCK-8, Transwell, Wound healing assay, flow cytometry and animal experiments verify the role of CASC19/miR-491-5p/HMGA2 regulatory axis.

RESULTS

The expression level of CASC19 is related to the T stage, N stage, and tumor size of patients. Knockdown of the expression of CASC19 can inhibit the ability of proliferation, migration, invasion and EMT conversion of GC cells, and knocking down the expression of CASC19 can promote the apoptosis of GC cells. Increasing the expression of miR-491-5p can inhibit the proliferation of GC cells, miR-491-5p mimics can inhibit EMT conversion, and promote the apoptosis of GC cells, while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of GC cells. The expression of HMGA2 in GC tissues is higher than that in adjacent tissues. At the same time, the expression level of HMGA2 is related to the N and T stages of the patients. Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of GC cells. Cell experiments and animal experiments have proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p, thereby affecting the biological functions of GC.

CONCLUSION

CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of GC. This axis may serve as a potential biomarker and therapeutic target of GC.

Keywords: Gastric cancer; Long non-coding RNA CASC19; miR-491-5p; HMGA2; Prognosis

Core Tip: Gastric cancer (GC) is a common malignant tumor, long non-coding RNA and microRNA are important regulators that affect tumor proliferation, metastasis and chemotherapy resistance, and thus participate in tumor progression, this study aim to explore the role of CASC19/miR-491-5p/HMGA2 regulatory axis in GC, this article verify that CASC19 may promote the progression of GC by regulating the miR-491-5p/HMGA2 signal axis, which can be helpful for the diagnosis and treatment of GC.