Research Paper Volume 13, Issue 8 pp 12067—12085
Expression profile, molecular functions, and prognostic significance of miRNAs in primary colorectal cancer stem cells
- 1 Institute of Digestive Surgery, Sichuan University, and Department of Gastrointestinal Surgery, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China
- 2 Department of Gastrointestinal Surgery and Breast and Thyroid Surgery, Minimally Invasive Surgery, West China Fourth Hospital, Sichuan University, Chengdu, China
- 3 Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
- 4 Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, Chengdu, China
- 5 School of Medicine, Institute of Medical Sciences, Örebro University, Örebro, Sweden
Received: October 19, 2020 Accepted: March 13, 2021 Published: April 1, 2021
https://doi.org/10.18632/aging.202914How to Cite
Copyright: © 2021 Fan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
MicroRNAs (miRNAs) are known to drive the pathogenesis of colorectal cancer (CRC) via the regulation of cancer stem cells (CSCs). We studied the miRNA expression profile of primary CSCs isolated from patients with CRC (pCRCSCs). Compared to pCRCSC-derived differentiated cells, 98 differentially expressed miRNAs were identified in pCRCSCs. Target genes encoding pCRCSC-related miRNAs were identified using a combination of miRNA target databases and miRNA-mRNA regulatory networks from the same patient. The pCRCSC-related miRNA target genes were associated with pathways contributing to malignant phenotypes, including I-kappa B kinase/NF-kappa B signaling, signal transduction by p53 class mediator, Ras signaling, and cGMP-PKG signaling. The pCRCSC-related miRNA expression signature was independently associated with poor overall survival in both the training and validation cohorts. We have thus identified several pCRCSC-related miRNAs with oncogenic potential that could serve as prognostic biomarkers for CRC.
Abbreviations
miRNAs: microRNAs; CSCs: cancer stem cells; CRC: colorectal cancer; pCRCSCs: primary CSCs from CRC patients; GO: gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; OS: overall survival.