miR-145 inhibits proliferation and invasion of esophageal squamous cell carcinoma in part by targeting c-Myc

Onkologie. 2013;36(12):754-8. doi: 10.1159/000356978. Epub 2013 Nov 20.

Abstract

Background: Accumulating evidence has shown that microRNAs (miRNAs) are aberrantly expressed in human esophageal cancer and crucial to tumorigenesis. Herein, we identified the role of miR-145 in esophageal squamous cell carcinoma (ESCC) development in vitro and in vivo.

Material and methods: miR-145 expression was investigated in 40 ESCC samples as well as 5 ESCC cell lines by real-time polymerase chain reaction. Crystal violet and transwell assays were conducted to explore the effects of miR-145 on the proliferation and invasion of human ESCC cell lines, respectively. The impact of overexpression of miR-145 on putative target c-Myc was subsequently confirmed via Western blot.

Results: miR-145 expression was frequently downregulated in ESCC specimens and cell lines compared with adjacent normal tissues (p < 0.05). Overexpression of miR-145 suppressed (p < 0.05) ESCC cell proliferation and invasion, as well as the growth of xenograft tumors in mice. Overexpression of miR-145 significantly decreased (p < 0.05) the protein level of c-Myc which has previously been identified as a direct target of miR-145.

Conclusion: Our results demonstrate that overexpression of miR-145 inhibits tumor growth in part by targeting c-Myc. Our findings revealed that miR-145 may act as a tumor suppressor in ESCC, and its dysregulation may be involved in the initiation and development of human ESCC.

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Gene Silencing / drug effects
  • Gene Targeting / methods
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / therapeutic use*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / prevention & control
  • Proto-Oncogene Proteins c-myc / genetics*
  • Treatment Outcome
  • Tumor Cells, Cultured

Substances

  • MIRN145 microRNA, human
  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc