Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Long noncoding RNA SNHG5 promotes 5-fluorouracil resistance in colorectal cancer by regulating miR-26b/p-glycoprotein axis
Bin Wang, Qian Zhou, Cui-E Cheng, Yi-Jie Gu, Ting-Wang Jiang, Jia-Ming Qiu, Gui-Ning Wei, Ya-Dong Feng, Li-Hua Ren, Rui-Hua Shi
Bin Wang, Ya-Dong Feng, Li-Hua Ren, Rui-Hua Shi, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
Bin Wang, Qian Zhou, Cui-E Cheng, Yi-Jie Gu, Department of Gastroenterology, The Affiliated Changshu Hospital of Nantong University, Changshu No. 2 People’s Hospital, Suzhou 215500, Jiangsu Province, China
Ting-Wang Jiang, Department of Key Laboratory, The Affiliated Changshu Hospital of Nantong University, Changshu No. 2 People’s Hospital, Suzhou 215500, Jiangsu Province, China
Jia-Ming Qiu, Department of Pathology, The Affiliated Changshu Hospital of Nantong University, Changshu No. 2 People’s Hospital, Suzhou 215500, Jiangsu Province, China
Gui-Ning Wei, Department of Pharmacology, Guangxi Institute of Chinese Medicine and Pharmaceutical Science, Nanning 530022, Guangxi Zhuang Autonomous Region, China
Ya-Dong Feng, Li-Hua Ren, Rui-Hua Shi, Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China
Author contributions: Wang B contributed to the conceptualization of the study, methodology, investigation, formal analysis, and writing and editing of the manuscript; Zhou Q, Gu YJ and Qiu JM contributed to the formal analysis and data curation; Cheng CE contributed to the conceptualization of the study and supervision; Jiang TW, Wei GN and Ren LH contributed to the methodology and validation; Feng YD contributed to the investigation and formal analysis; Shi RH contributed to the conceptualization of the study, supervision, writing, review and editing; All authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82404088; China Postdoctoral Science Foundation, No. 2023M730587; and Changshu Talent Scientific Project, No. KCH202304.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board Changshu No. 2 People’s Hospital (No. 2020-KY-008).
Institutional animal care and use committee statement: The animal experiments were approved by the Animal Care and Welfare Committee of Southeast University (No. 20200721007).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The data generated or analyzed during this study are available from the corresponding author upon reasonable request.
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: Rui-Hua Shi, MD, Professor, School of Medicine, Southeast University, No. 87 Dingjiaqiao Road, Gulou District, Nanjing 210009, Jiangsu Province, China.
ruihuashi@126.com
Received: October 18, 2024
Revised: February 3, 2025
Accepted: February 27, 2025
Published online: May 15, 2025
Processing time: 209 Days and 15.4 Hours
BACKGROUND
Colorectal cancer (CRC) is the second most prevalent cause of cancer-related mortality and is increasing in younger individuals. Chemotherapy, a crucial adjuvant systemic therapy for CRC management, often leads to resistance through poorly characterized underlying molecular mechanisms. The long noncoding RNA SNHG5 is highly expressed in CRC and promotes tumor proliferation and invasion, prompting us to hypothesize that SNHG5 may play a crucial role in the chemotherapeutic agent 5-fluorouracil (5-Fu) resistance in CRC.
AIM
To identify the function and mechanism of SNHG5 in 5-Fu resistance in CRC.
METHODS
Quantitative real-time polymerase chain reaction was performed to examine the expression of SNHG5 in CRC tissues from 22 5-Fu-sensitive patients and 14 5-Fu-resistant patients and in CRC cells and 5-Fu-resistant CRC cells. Cell viability and apoptosis were assessed in SNHG5-overexpressing CRC cells and SNHG5-knockdown 5-Fu-resistant CRC cells. SNHG5 function in 5-Fu resistance in CRC was further analyzed using a xenograft mouse model. SNHG5 interactions with microRNAs were predicted by bioinformatics analysis. Luciferase reporter and RNA immunoprecipitation assays were performed to verify the binding between SNHG5 and miR-26b. Rescue experiments were performed to validate the functional interaction between SNHG5 and the miR-26b/p-glycoprotein (Pgp) axis.
RESULTS
SNHG5 expression was upregulated in 5-Fu-resistant CRC tissues and 5-Fu-resistant CRC cells. In vitro functional experiments demonstrated that SNHG5 overexpression significantly reduced cell apoptosis and enhanced cell viability, whereas SNHG5 knockdown in 5-Fu-resistant CRC cells increased cell apoptosis and decreased cell viability upon 5-Fu treatment. In a xenograft mouse model, we confirmed that SNHG5 overexpression led to a reduction in 5-Fu sensitivity in CRC in vivo. Mechanistically, SNHG5 acted as a molecular sponge for miR-26b. Rescue experiments validated that SNHG5 conferred 5-Fu resistance in CRC by regulating the miR-26b/Pgp axis.
CONCLUSION
SNHG5/miR-26b/Pgp regulates CRC chemosensitivity, providing potential therapeutic targets for the treatment of 5-Fu-resistant CRC.
Core Tip: This study confirmed that the expression of the long noncoding RNA SNHG5 was upregulated in 5-fluorouracil (5-Fu)-resistant colorectal cancer (CRC) tissues and 5-Fu-resistant CRC cells. Functional experiments confirmed that SNHG5 overexpression reduced 5-Fu sensitivity in CRC in vitro and in vivo. Mechanistically, SNHG5 acted as a molecular sponge for miR-26b. In addition, SNHG5 conferred 5-Fu resistance in CRC by regulating the miR-26b/p-glycoprotein axis. Our results elucidate potential mechanisms of noncoding RNAs in CRC chemoresistance and provide new strategies for CRC chemotherapy.
