Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2025; 31(16): 104305
Published online Apr 28, 2025. doi: 10.3748/wjg.v31.i16.104305
LncRNA FTX promotes colorectal cancer radioresistance through disturbing redox balance and inhibiting ferroptosis via miR-625-5p/SCL7A11 axis
Qing Dai, Tian-Yin Qu, Jin-Lan Yang, Jing Leng, Lin Fang, Qian-Qian Zhu, Ke-Bi Wu, Jie Wu, Jing-Jing Ma, Huang-Fei Yu
Qing Dai, Tian-Yin Qu, Jin-Lan Yang, Jing Leng, Lin Fang, Qian-Qian Zhu, Ke-Bi Wu, Huang-Fei Yu, Department of Oncology, Cancer Disease Research Institute, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi 563000, Guizhou Province, China
Jie Wu, Scientific Research Center, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi 563000, Guizhou Province, China
Jing-Jing Ma, Department of Clinical Laboratory, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi 563000, Guizhou Province, China
Co-corresponding authors: Jing-Jing Ma and Huang-Fei Yu.
Author contributions: Ma JJ and Yu HF contribute equally to this study as co-corresponding authors; Dai Q performed all the experiments; Qu TY and Ma JJ provided methodology; Yang JL, Leng J, Fang L, Zhu QQ, Wu KB and Wu J collected, analyzed, and interpreted data; Yu HF designed this study; Dai Q, Ma JJ and Yu HF prepared this manuscript; all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81960506; Science and Technology Fund Project of Guizhou Provincial Health Commission, No. gzwkj2022-299; and Key Projects of Zunyi Science and Technology Fund, No. zunshikeheHZzi(2023)24 and No. zunshikeheHZzi(2024)9.
Institutional review board statement: This study was approved by the Institutional Review Board at the Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), approval No. 2023-1-209.
Institutional animal care and use committee statement: All animal experiments were approved by the Animal Care and Use Committee of the Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi; No. 2024-2-723).
Conflict-of-interest statement: All authors declare no conflicts 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: All the data obtained in the current study are available from the corresponding authors 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: Huang-Fei Yu, MD, Department of Oncology, Cancer Disease Research Institute, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), No. 98 Fenghuang Road, Zunyi 563000, Guizhou Province, China. huangfeiyu@zmu.edu.cn
Received: December 19, 2024
Revised: February 23, 2025
Accepted: March 27, 2025
Published online: April 28, 2025
Processing time: 130 Days and 23 Hours
Abstract
BACKGROUND

Radiotherapy is widely employed in colorectal cancer (CRC) treatment, but the occurrence of radioresistance severely limits the clinical benefit to patients and significantly contributes to treatment failure and recurrent metastasis.

AIM

To explore the role and underlying mechanism of the lncRNA FTX in radiotherapy resistance in CRC.

METHODS

LncRNA FTX expression in colorectal parent cells (HT29 and HCT116) and radioresistant cells (HT29R and HCT116R) was determined by real-time quantitative PCR, and the viability of HT29R-shFTX and HCT116R-shFTX cells under ionizing radiation was evaluated using the cell counting kit-8 assay and colony formation experiment. The levels of glutathione and reactive oxygen species in cells after irradiation were determined, and the association between ferroptosis and lncRNA FTX expression in cancer cells was tested. A dual-luciferase assay was used to validate gene interactions. A xenotransplantation mouse model was established to explore the effects of FTX on the CRC tumor radiosensitivity in vivo.

RESULTS

FTX was upregulated in radioresistant CRC cells, and FTX knockdown inhibited cell survival and increased cell ferroptotic death in response to ionizing radiation. Moreover, lncRNA FTX restricted the SLC7A11 expression by sponging with miR-625-5p, and inhibition of the lncRNA FTX or SLC7A11 significantly increased cellular oxidant levels and DNA damage to ionizing radiation in cancer cells. However, SLC7A11 overexpression reversed the effects of decreased FTX levels on ferroptosis and high oxidation levels in cancer cells exposed to ionizing radiation.

CONCLUSION

Inhibition of the lncRNA FTX/miR-625-5p/SLC7A11 axis can induce ferroptosis and disturb intracellular redox balance, further sensitizing CRC cells to ionizing radiation, suggesting its potential as a therapeutic target for improving CRC response to radiation therapy.

Keywords: Colorectal cancer; LncRNA FTX; Solute carrier family 7 member 11; Ferroptosis; Redox; Radioresistance

Core Tip: Radiotherapy is widely employed in colorectal cancer (CRC) treatment, but the occurrence of radioresistance severely limits the clinical benefit to patients and significantly contributes to treatment failure and recurrent metastasis. In this study, our results demonstrated that inhibition of the lncRNA FTX/miR-625-5p/SLC7A11 axis can induce ferroptosis and disturb intracellular redox balance, further sensitizing CRC cells to ionizing radiation, suggesting its potential as a therapeutic target for improving CRC response to radiation therapy.