Expression profile, molecular functions, and prognostic significance of miRNAs in primary colorectal cancer stem cells

Aging (Albany NY). 2021 Apr 1;13(8):12067-12085. doi: 10.18632/aging.202914. Epub 2021 Apr 1.

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.

Keywords: cancer stem cells; colorectal cancer; miRNAs; prognosis; progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Animals
  • Biomarkers, Tumor / metabolism*
  • Colectomy
  • Colon / pathology
  • Colon / surgery
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • MicroRNAs / metabolism*
  • Middle Aged
  • Models, Genetic*
  • Neoplastic Stem Cells / metabolism*
  • Predictive Value of Tests
  • Primary Cell Culture
  • Prognosis
  • RNA, Messenger / genetics
  • Risk Assessment / methods
  • Signal Transduction / genetics
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Messenger