Downregulation of miR-218-5p promotes invasion of oral squamous cell carcinoma cells via activation of CD44-ROCK signaling

Biomed Pharmacother. 2018 Oct:106:646-654. doi: 10.1016/j.biopha.2018.06.151. Epub 2018 Jul 11.

Abstract

The invasion front of oral squamous cell carcinoma (OSCC) harbors the most aggressive cells of the tumor and is critical for cancer invasion and metastasis. MicroRNAs (miRNAs) play important roles in OSCC progression. In this study, we modelled the OSCC invasion front on a microfluidic chip, and investigated differences in miRNA profiles between cells in the invasion front and those in the tumor mass by small RNA sequencing. We found that miR-218-5p was downregulated in invasion front cells and negatively regulates OSCC invasiveness by targeting the CD44-ROCK pathway. Thus, miR-218-5p may serve as a useful therapeutic target for OSCC. Moreover, invasion front cell isolation based-on microfluidic technology provided a useful strategy for cancer invasion study.

Keywords: CD44; Invasion; Microfluidic chip; OSCC; ROCK; miR-218-5p.

MeSH terms

  • Cell Movement*
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Lab-On-A-Chip Devices
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microfluidic Analytical Techniques / instrumentation
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / enzymology
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck / drug therapy*
  • Squamous Cell Carcinoma of Head and Neck / enzymology
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Time Factors
  • rho-Associated Kinases / metabolism*

Substances

  • CD44 protein, human
  • Hyaluronan Receptors
  • MIRN218 microRNA, human
  • MicroRNAs
  • rho-Associated Kinases