MicroRNA-29b regulates migration in oral squamous cell carcinoma and its clinical significance

Oral Oncol. 2015 Feb;51(2):170-7. doi: 10.1016/j.oraloncology.2014.10.017. Epub 2014 Nov 27.

Abstract

Objectives: MicroRNA (miRNA) machinery regulates cancer cell behavior, and has been implicated in patients' clinical status and prognosis. We found that microRNA-29b (miR-29b) increased significantly in advanced migratory cells. However, miR-29b controls the migration ability, and its regulatory mechanism in oral squamous cell carcinoma (OSCC) remains unknown.

Materials and methods: We triggered miR-29b expression in OSCC patients and cell lines by conducting real-time quantitative PCR. We determined the functions of miR-29b in the migration of OSCC cells by using gain- and loss-of-function approaches. We elevated the target genes of miR29b through software predictions and a luciferase report assay. We used an orthotopic OSCC animal model to investigate the effects of miR29b on OSCC cell metastasis in vivo.

Results: The clinical data revealed that miR-29b expression was correlated with lymph node metastasis and an advanced tumor stage in 98 OSCC patients. Furthermore, multivariate analysis revealed that miR-29b expression was significantly correlated with recurrence, and indicated poor survival. MiR-29b promoted OSCC cell migration and downregulated CX3CL1, a cell-cell adhesion regulator, which plays an essential role in miR-29b-regulated OSCC cell migration machinery. Furthermore, we found that CX3CL1 expression was correlated with lymph node metastasis and an early tumor stage in OSCC patients, and negatively correlated with miR-29b expression.

Conclusion: MiR-29b acts as an oncomir, promoting cell migration through CX3CL1 suppression, and could be a potential therapeutic target for preventing OSCC progression.

Keywords: CX3CL1; Migration; Oral cancer; miR-29b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / pathology*
  • Chemokine CX3CL1 / genetics
  • Gene Silencing
  • Humans
  • Lymphatic Metastasis
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Mouth Neoplasms / pathology*
  • Neoplasm Metastasis*
  • Survival Analysis

Substances

  • Chemokine CX3CL1
  • MIRN29a microRNA, human
  • MicroRNAs