Li GB, Shi WK, Zhang X, Qiu XY, Lin GL. Hsa-miR-483-5p/mRNA network that regulates chemotherapy resistance in locally advanced rectal cancer identified through plasma exosome transcriptomics. World J Clin Oncol 2024; 15(8): 1061-1077 [PMID: 39193162 DOI: 10.5306/wjco.v15.i8.1061]
Corresponding Author of This Article
Guo-Le Lin, MD, PhD, Surgeon, Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China. linguole@126.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Clinical and Translational Research
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Aug 24, 2024; 15(8): 1061-1077 Published online Aug 24, 2024. doi: 10.5306/wjco.v15.i8.1061
Hsa-miR-483-5p/mRNA network that regulates chemotherapy resistance in locally advanced rectal cancer identified through plasma exosome transcriptomics
Gan-Bin Li, Wei-Kun Shi, Xiao Zhang, Xiao-Yuan Qiu, Guo-Le Lin
Gan-Bin Li, Wei-Kun Shi, Xiao Zhang, Xiao-Yuan Qiu, Guo-Le Lin, Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China
Author contributions: Li GB, Shi WK and Lin GL conceptualized and designed the research; Li GB, Shi WK, Zhang X, Qiu XY, and Lin GL screened patients and acquired clinical data; Li GB and Shi WK collected the clinical data; Li GB performed data analysis; Li GB, and Shi WK wrote the paper; Lin GL conceptualized, designed, and supervised the whole process of the project; Li GB and Qiu XY 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; All authors have read and approved the final manuscript.
Supported bythe National High Level Hospital Clinical Research Funding, No. 2022-PUMCH-C-005.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Guo-Le Lin, MD, PhD, Surgeon, Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China. linguole@126.com
Received: April 28, 2024 Revised: July 10, 2024 Accepted: July 25, 2024 Published online: August 24, 2024 Processing time: 109 Days and 16.4 Hours
Abstract
BACKGROUND
Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy (nCRT) for rectal cancer. However, the underlying mechanisms remain elusive.
AIM
To detect the differential expression profiles of plasma exosomal microRNAs (miRNAs) in poor and good responders and explore the potential mechanisms of chemoresistance.
METHODS
In this study, the profiles of plasma exosomal miRNAs were compared in two dimensions according to treatment responses (poor/good responders) and treatment courses (pre/post-nCRT) using RNA sequencing.
RESULTS
Exosome hsa-miR-483-5p was up-regulated in good responders post-nCRT. Bioinformatics analysis revealed that the target genes of hsa-miR-483-5p were mainly enriched in tumor-specific pathways, such as the MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, Toll-like receptor signaling pathway, VEGF signaling pathway, and mTOR signaling pathway. Further analysis indicated that MAPK3, RAX2, and RNF165 were associated with inferior recurrence-free survival in patients with rectal cancer, and the profiles of MAPK3, TSPYL5, and ZNF417 were correlated with tumor stage. In addition, the expression profiles of MAPK3, RNF165, and ZNF417 were negatively correlated with inhibitory concentration 50 values. Accordingly, an hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 network was constructed.
CONCLUSION
This study provides insights into the mechanism of chemoresistance in terms of exosomal miRNAs. However, further research is required within the framework of our established miRNA-mRNA network.
Core Tip: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for the management of locally advanced rectal cancer; however, chemoresistance remains a life-threatening problem in patients with colorectal cancer. In this study, we used RNA sequencing to identify the expression profiles of plasma exosomal microRNAs (miRNAs) in two dimensions, according to treatment response (poor/good responders) and treatment course (pre/post-nCRT). Exosome hsa-miR-483-5p was upregulated in good responders post-nCRT and was chosen for further analysis. A network of hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 was constructed using bioinformatic analysis in terms of survival, stage, and drug sensitivity. This study provides insights into the mechanism of chemoresistance in terms of exosomal miRNAs. However, further research is required within the framework of our established miRNA-mRNA network.
