Alteration of microRNA-4474/4717 expression and CREB-binding protein in human colorectal cancer tissues infected with Fusobacterium nucleatum

PLoS One. 2019 Apr 5;14(4):e0215088. doi: 10.1371/journal.pone.0215088. eCollection 2019.

Abstract

Colorectal cancer (CRC) is a common and highly lethal form of cancer. Although the etiologic role of Fusobacterium nucleatum (F. nucleatum) in the development of CRC has been elucidated, the specific tumor molecules involved in the progression of CRC induced by F. nucleatum have not been identified. This study investigated several miRNAs and genes involved in the progression of F. nucleatum-induced CRC by Affymetrix miRNA microarray technology and GeneChip Human Transcriptome Array 2.0. The results suggest that miR-4474 and miR-4717 are up-regulated in CRC tissues in response to F. nucleatum infection, compared with the control group (paracancerous tissues), while other genes associated with signaling pathways in cancer, including CREB-binding protein (CREBBP), STAT1, PRKACB, CAMK2B, JUN, TP53 and EWSR1, were dysregulated. Bioinformatic analysis identified CREBBP as the primary aberrantly expressed gene in F. nucleatum-induced CRC. Consistent with the microarray analysis results, real-time RT-PCR analysis demonstrated that the expression of miR-4474/4717 was upregulated while that of CREBBP mRNA was downregulated in CRC patients infected with F. nucleatum. Additionally, CREBBP was identified as a novel target of miR-4474/4717. The results of this study suggest that miR-4474 and miR-4717 are involved in the progression of F. nucleatum-induced CRC by posttranscriptionally regulating the target gene CREBBP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CREB-Binding Protein / genetics
  • CREB-Binding Protein / metabolism*
  • Case-Control Studies
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / microbiology
  • Colorectal Neoplasms / pathology
  • Female
  • Fusobacterium Infections / complications*
  • Fusobacterium Infections / epidemiology
  • Fusobacterium Infections / microbiology
  • Fusobacterium nucleatum / isolation & purification*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Signal Transduction
  • Young Adult

Substances

  • MIRN4474 microRNA, human
  • MIRN4717 microRNA, human
  • MicroRNAs
  • CREB-Binding Protein
  • CREBBP protein, human

Grants and funding

Funding was provided by the Young Scientists Fund (CN), grant no. 81501796, to QL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.