Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2024; 16(4): 1453-1464
Published online Apr 15, 2024. doi: 10.4251/wjgo.v16.i4.1453
MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A
Mei-Zhu Shen, Yong Zhang, Fang Wu, Mei-Zhen Shen, Jun-Lin Liang, Xiao-Long Zhang, Xiao-Jian Liu, Xin-Shu Li, Ren-Sheng Wang
Mei-Zhu Shen, Yong Zhang, Fang Wu, Ren-Sheng Wang, Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Mei-Zhen Shen, Department of Radiotherapy, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Jun-Lin Liang, Xiao-Long Zhang, Xiao-Jian Liu, Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Xin-Shu Li, Department of Clinical Medicine, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Author contributions: Shen MZ, Zhang Y, and Wang RS conceived and designed the experiments; Wu F, Shen MZ, Liang JL, Zhang XL, Liu XJ, and Li XS performed the experiments; Shen MZ and Wang RS analyzed the data and wrote the manuscript; all authors read and approved the final manuscript.
Institutional animal care and use committee statement: This study was reviewed and approved by the Experimental Animal Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (Approval No. 2023-E386-01).
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The datasets generated and analyzed during the current study are available from the corresponding author on reasonable 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: Ren-Sheng Wang, PhD, Doctor, Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Qingxiu District, Nanning 530021, Guangxi Zhuang Autonomous Region, China. 13807806008@163.com
Received: December 5, 2023
Peer-review started: December 5, 2023
First decision: December 18, 2023
Revised: December 31, 2023
Accepted: February 2, 2024
Article in press: February 2, 2024
Published online: April 15, 2024
ARTICLE HIGHLIGHTS
Research background

Radiotherapy stands as a promising therapeutic modality for colorectal cancer (CRC); yet, the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission.

Research motivation

Radiotherapy can effectively inhibit the proliferation of cancer cells, but a considerable number of CRC patients are still resistant to radiotherapy, and further exploration of potential drug resistance targets is needed to provide a theoretical basis for developing effective treatment strategies to improve response rate.

Research objectives

To analyze the role of microRNA-298 (miR-298) in the radioresistance of CRC and its molecular mechanism. MiRNAs are involved in a wide range of physiological and pathological processes, and the dysregulation of miR-298 has been shown to be related to the development of CRC. However, the exact role that miR-298 plays in the radioresistance of CRC cells remains to be elucidated.

Research methods

This study established a radiation-resistant CRC cell line, which exposes HT-29 cells to 5 gray ionizing radiation, followed by a 7-d recovery period. The miR-298 expression level and the biological behavior of HT-29 cells were examined before and after radiotherapy. To explore the radiosensitivity and the expression of downstream target genes in ectopic CRC model tumors after overexpressing miR-298. Dual-luciferase reporter assay for the binding site of DYRK1A with miR-298. Knockdown of miR-298 observed DYRK1A expression and radiation-induced apoptosis were improved in HT-29 cells.

Research results

We observed a significant upregulation of miR-298 in radioresistant CRC cells. MiR-298 emerged as a key determinant of cell survival after radiation exposure, as its overexpression resulted in a significant reduction in radiation-induced apoptosis. Interestingly, there was a strong correlation between miR-298 expression and CRC cell viability. Further studies revealed DYRK1A as a direct target of miR-298. Taken together, our results highlight the role that miR-298 plays in enhancing radioresistance in CRC cells by downregulation of DYRK1A, thereby positioning miR-298 as a promising candidate gene.

Research conclusions

This study revealed an important target of CRC resistance to radiotherapy, miR-298, an effect of DYRK1A to enhance radioresistance in CRC cells. This study provides proof of principle for the development of a protocol based on radiotherapy + targeting for CRC.

Research perspectives

Cancer radiotherapy resistance remains a major challenge for cancer patients. To improve patient outcomes, we need to further understand the mechanisms by which tumor ecosystem tumor cell proliferation, apoptosis, invasion, and migration under the induction of continuous therapy. Analysis of the targets of radiotherapy sensitive/resistant to tumors will help to discover new therapeutic opportunities.