MicroRNA-6869-5p acts as a tumor suppressor via targeting TLR4/NF-κB signaling pathway in colorectal cancer

J Cell Physiol. 2018 Sep;233(9):6660-6668. doi: 10.1002/jcp.26316. Epub 2018 Mar 25.

Abstract

Many studies have implicated that microRNAs (miRNAs), as non-coding RNAs, play important roles in the development and progression of colorectal cancer (CRC). However, little is known about the role of a newly identified miRNA, miR-6869-5p, in CRC. We aim to investigate the modifying effects and underlying mechanisms of miR-6869-5 in colorectal carcinogenesis and progression. Significantly reduced levels of miR-6869-5p were observed in both serum exosomes tumor tissue samples from patients with CRC. The prediction of targets of miR-6869-5p in databases of targetscan, microRNA. ORG and miRDBA revealed that toll-like receptor 4 (TLR4) is a potential target for this miRNA. MiR-6869-5p could inhibit cell proliferation and the production of inflammatory cytokines (TNF-α and IL-6) in CRC cells via directly targeting TLR4. The protective effect of miR-6869-5p from colorectal carcinogenesis was dependent on TLR4/NF-κB signaling pathway. In addition, the 3-year survival was poor among CRC patients with decreased levels of miR-6869-5p in serum exosomes. Thus, miR-6869-5p may serve as a tumor suppressor in CRC, and serum exosomal miR-6869-5p is a promising circulating biomarker for the prediction of CRC prognosis.

Keywords: NF-κB; TLR4; colorectal cancer; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Exosomes / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • HCT116 Cells
  • HEK293 Cells
  • Humans
  • Inflammation / genetics
  • Inflammation / pathology
  • Interleukin-6 / genetics
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • NF-kappa B / genetics*
  • Prognosis
  • Retrospective Studies
  • Signal Transduction / genetics*
  • Toll-Like Receptor 4 / genetics*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Biomarkers, Tumor
  • Interleukin-6
  • MicroRNAs
  • NF-kappa B
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha