miR-200c-3p spreads invasive capacity in human oral squamous cell carcinoma microenvironment

Mol Carcinog. 2018 Feb;57(2):295-302. doi: 10.1002/mc.22744. Epub 2017 Oct 31.

Abstract

Oral squamous cell carcinoma (OSCC) constitutes over 90% of all cancers in the oral cavity. The prognosis for patients with invasive OSCC is poor; therefore, it is important to understand the molecular mechanisms of invasion and subsequent metastasis not only to prevent cancer progression but also to detect new therapeutic targets against OSCC. Recently, extracellular vesicles-particularly exosomes-have been recognized as intercellular communicators in the tumor microenvironment. As exosomic cargo, deregulated microRNAs (miRNAs) can shape the surrounding microenvironment in a cancer-dependent manner. Previous studies have shown inconsistent results regarding miR-200c-3p expression levels in OSCC cell lines, tissues, or serum-likely because of the heterogeneous characters of the specimen materials. For this reason, single-cell clone analyses are necessary to effectively assess the role of exosome-derived miRNAs on cells within the tumor microenvironment. The present study utilized integrated microarray profiling to compare exosome-derived miRNA and exosome-treated cell-derived mRNA expression. Data were acquired from noninvasive SQUU-A and highly invasive SQUU-B tongue cancer cell clones derived from a single patient to determine candidate miRNAs that promote OSCC invasion. Matrigel invasion assays confirmed that hsa-miR-200c-3p was a key pro-invasion factor among six miRNA candidates. Consistently, silencing of the miR-200c-3p targets, CHD9 and WRN, significantly accelerated the invasive potential of SQUU-A cells. Thus, our data indicate that miR-200c-3p in exosomes derived from a highly invasive OSCC line can induce a similar phenotype in non-invasive counterparts.

Keywords: invasion; microRNA; microarray; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Exosomes / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs / genetics*
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Signal Transduction / genetics
  • Tumor Microenvironment / genetics*

Substances

  • MIRN200 microRNA, human
  • MicroRNAs