circRNA_100859 functions as an oncogene in colon cancer by sponging the miR-217-HIF-1α pathway

Aging (Albany NY). 2020 Jul 8;12(13):13338-13353. doi: 10.18632/aging.103438. Epub 2020 Jul 8.

Abstract

Circular RNAs (circRNAs) play an important role in cancer development and progression by regulating gene expression. The present study aimed to investigate the function of circRNA_100859 in colon cancer. circRNA expression profiles from a human circRNAs chip were analyzed. The effects of circRNA_100859 on cell proliferation and apoptosis were assessed in vitro and interactions between circRNA_100859 and its micro (mi)RNA and target genes were analyzed. The diagnostic and prognostic significance of circRNA_100859 was also investigated. It was identified that circRNA_100859 was overexpressed in colon cancer tissues and promoted cell proliferation and inhibited cell apoptosis. Additionally, bioinformatics and a dual-luciferase reporter assay confirmed that circRNA_100859 acted as a miR-217 sponge, and miR-217 directly targeted hypoxia-inducible factor (HIF)-1α. Rescue assays demonstrated that HIF-1α protein and mRNA expression levels and cell proliferation were regulated by the circRNA_100859/miR-217 axis (P<0.05). Furthermore, statistical analysis showed that the circRNA_100859-miR-217-HIF-1α axis was associated with Tumor-Node-Metastasis (TNM) stage, histological grade, and KRAS mutations, and also showed high diagnostic and prognostic value for patients with colon cancer (P<0.05). Therefore, it was concluded that circRNA_100859 functions as an oncogene in colon cancer by sponging the miR-217-HIF-1α pathway. In addition, the circRNA_100859-miR-217-HIF-1α axis may serve as a novel diagnostic and prognostic biomarker for patients with colon cancer.

Keywords: HIF-1α; biomarker; circRNA_100859; colon cancer; microRNA-217.

Publication types

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

MeSH terms

  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis / genetics*
  • Cell Proliferation / genetics
  • Colectomy
  • Colon / pathology
  • Colon / surgery
  • Colonic Neoplasms / diagnosis
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / surgery
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Kaplan-Meier Estimate
  • MicroRNAs / metabolism*
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Oncogenes
  • Prognosis
  • Progression-Free Survival
  • RNA, Circular / metabolism*

Substances

  • Biomarkers, Tumor
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN217 microRNA, human
  • MicroRNAs
  • RNA, Circular