Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2024; 16(10): 4194-4208
Published online Oct 15, 2024. doi: 10.4251/wjgo.v16.i10.4194
Long noncoding RNA steroid receptor RNA activator 1 inhibits proliferation and glycolysis of esophageal squamous cell carcinoma
Ming He, Ye Qi, Ze-Mao Zheng, Min Sha, Xiang Zhao, Yu-Rao Chen, Zheng-Hai Chen, Rong-Yu Qian, Juan Yao, Zheng-Dong Yang
Ming He, Ze-Mao Zheng, Xiang Zhao, Yu-Rao Chen, Rong-Yu Qian, Juan Yao, Department of Radiation Oncology, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
Ye Qi, Department of Nursing, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
Min Sha, Institute of Clinical Medicine, Taizhou People's Hospital Affiliated of Nantong University of Medicine, Taizhou 225300, Zhejiang Province, China
Zheng-Hai Chen, Zheng-Dong Yang, Department of Thoracic Surgery, Huai’an Hospital of Huai’an, Huai’an 223299, Jiangsu Province, China
Co-first authors: Ming He and Ye Qi.
Co-corresponding authors: Juan Yao and Zheng-Dong Yang.
Author contributions: He M, Qi Y, Zheng ZM, Yao J and Yang ZD conceptualized and designed the research; He M, Qi Y, Sha M and Yao J screened patients and acquired clinical data; He M, Qi Y, Zheng ZM, Qian RY and Yao J collected tissue specimen and performed the research; He M, Zhao X, Chen YR and Chen ZH performed data analysis; He M, Qi Y, Zheng ZM and Yao J wrote the paper. All the authors have read and approved the final manuscript. He M proposed, designed and conducted tissue specimen collection, performed data analysis and prepared the first draft of the manuscript. Qi Y was responsible for patient screening, enrollment, collection of clinical data and tissue specimens. Both authors have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper. Both Yao J and Yang ZD have played important and indispensable roles in the experimental design, data interpretation and manuscript preparation as the co-corresponding authors. Yao J applied for and obtained the funds for this research project. Yao J conceptualized, designed, and supervised the whole process of the project. She searched the literature, revised and submitted the early version of the manuscript. Yang ZD was instrumental and responsible for data re-analysis and re-interpretation, figure plotting, comprehensive literature search, preparation and submission of the current version of the manuscript. This collaboration between Yao J and Yang ZD is crucial for the publication of this manuscript.
Supported by Innovative Team of Jiangsu Province, No. CXTDA2017042; Jiangsu Provincial Medical Youth Talent, No. QNRC2016508; and In-Hospital Project of Taizhou People's Hospital, No. ZL201930.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Huai’an Hospital of Huai’an Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Ethical Committees of Huai’an Hospital of Huai’an (IACUC protocol No. 2016.A023).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at tzsry110120@163.com.
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: Juan Yao, MD, Chief Doctor, Department of Radiation Oncology, Huai’an Hospital of Huai’an, No. 19 Shanyang Avenue, Huai’an District, Huai’an 223299, Jiangsu Province, China. tzsry110120@163.com
Received: January 8, 2024
Revised: June 9, 2024
Accepted: June 28, 2024
Published online: October 15, 2024
Processing time: 261 Days and 21.8 Hours
Abstract
BACKGROUND

The clinical effects and detailed roles of long non-coding RNA (LncRNA) steroid receptor RNA activator 1 (SRA1) in esophageal squamous cell carcinoma (ESCC) remain ambiguous. In the present study, the complementary sites between lncRNA SRA1, miRNA-363-5p, and phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.

AIM

To investigate the molecular events of SRA1 in the malignant behavior in ESCC.

METHODS

Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired. SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction. Cell counting Kit-8 assay, transwell invasion assay, glycolysis assay, and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1. The t-test and the χ2 test were used for comparison between groups. Survival curve analysis was performed using the Kaplan-Meier method.

RESULTS

SRA1 downregulation was identified in ESCC. ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression. The introduction of SRA1 inhibited cell proliferation, glucose uptake, and lactate production in ESCC. In vivo, the growth of ESCC was hindered by SRA1 overexpression. Then, SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p. Lastly, the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.

CONCLUSION

SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis. The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.

Keywords: Steroid receptor RNA activator 1; Esophageal squamous cell carcinoma; Phospholysine phosphohistidine inorganic pyrophosphate phosphatase; Cancer therapy; MicroRNA; Long non-coding RNA

Core Tip: In this study, we identified abnormal expression of steroid receptor RNA activator 1 (SRA1) in esophageal squamous cell carcinoma (ESCC). SRA1 was significantly downregulated in ESCC tissues and cell lines, and its low expression was strongly associated with advanced tumor stage, metastasis, larger tumor size, and poor survival. Functional and rescue assays demonstrated that SRA1 could impede ESCC cell proliferation and glycolysis via miRNA-363-5p and phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP). Mechanistically, SRA1 elevated LHPP expression by sponging miRNA-363-5p, thereby inhibiting ESCC cell proliferation and glycolysis.