MicroRNA-155-5p is associated with oral squamous cell carcinoma metastasis and poor prognosis

J Oral Pathol Med. 2016 Apr;45(4):248-55. doi: 10.1111/jop.12351. Epub 2015 Aug 26.

Abstract

Background: Abnormal miRNA expression was recently implicated in the metastasis of oral squamous cell carcinoma (OSCC) and with a poor prognosis. The initiation of the invasion-metastasis cascade involves epithelial-mesenchymal transition (EMT). Our aim was to clarify how miRNA, especially miR-155-5p misexpression contributes to OSCC metastasis through EMT.

Methods: We collected tumor samples from 73 subjects with OSCC. The samples were analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and correlations between miR-155-5p levels and clinical characteristics were investigated. OSCC cell lines were analyzed by miRNA microarray and by transfection with a miR-155-5p mimic or inhibitor, followed by proliferation and wound-healing migration assays. qRT-PCR analyses of EMT makers in cells transfected with miR-155-5p inhibitor were performed.

Results: We found high miR-155-5p expression in tissue samples from subjects with OSCC that had metastasized to cervical lymph nodes. HSC-3 cells also strongly expressed miR-155-5p. The epithelial marker E-cadherin was strongly expressed in HSC-3 cells transfected with miR-155-5p inhibitor, and we observed elevated SOCS1 and decreased STAT3 expression in these cells.

Conclusions: Our results suggest that miR-155-5p causes OSCC to metastasize, and could serve as a novel therapeutic target for OSCC.

Keywords: epithelial mesenchymal transition; metastasis; miR-155; microRNA; oral cancer.

MeSH terms

  • Antigens, CD
  • Biomarkers, Tumor / genetics
  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition
  • Female
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology
  • Humans
  • Lymph Nodes
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Neoplasm Metastasis
  • Prognosis
  • STAT3 Transcription Factor / biosynthesis
  • STAT3 Transcription Factor / genetics
  • Squamous Cell Carcinoma of Head and Neck
  • Suppressor of Cytokine Signaling 1 Protein / biosynthesis
  • Suppressor of Cytokine Signaling 1 Protein / genetics
  • Transfection

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CDH1 protein, human
  • Cadherins
  • MIRN155 microRNA, human
  • MicroRNAs
  • SOCS1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Suppressor of Cytokine Signaling 1 Protein