MiR-330-5p regulates tyrosinase and PDIA3 expression and suppresses cell proliferation and invasion in cutaneous malignant melanoma

J Surg Res. 2016 Jun 15;203(2):434-40. doi: 10.1016/j.jss.2016.03.021. Epub 2016 Mar 19.

Abstract

Background: Increasing evidence has suggested that miR-330-5p can function as a tumor suppressor in different types of cancers. However, the effects and underlying mechanisms of miR-330-5p in the development of cutaneous malignant melanoma (CMM) remain largely unknown. The aim of the present study was to investigate the role of miR-330-5p in CMM and to determine the molecular mechanisms underlying its action.

Materials and methods: The expression level of miR-330-5p was detected in 26 cases of primary CMM tissues and cell lines by real-time quantitative polymerase chain reaction. We also assessed whether overexpression of miR-330-5p influences in vitro cell proliferation, invasion, and migration. Western blotting analysis was used to detect the influence of miR-330-5p on the targets, and Pearson analysis was used to calculate the correlation between the expression of targets gene and miR-330-5p in CMM tissues.

Results: Our study showed that miR-330-5p was downregulated in CMM tissues (P = 0.010) and cell lines (P < 0.05), and patients with high mitotic activity showed lower miR-330-5p expression levels (P = 0.002). Enforced expression of miR-330-5p inhibits malignant CMM cells proliferation and migration and led to downregulation of the TYR and PDIA3 protein. Moreover, the expression level of miR-330-5p in CMM tissues showed inverse relationship with the expression level of TYR and PDIA3 protein.

Conclusions: In conclusion, our findings suggested that miR-330-5p represents a potential tumor-suppressive miRNA and plays an important role in CMM progression by suppressing TYR and PDIA3 expression.

Keywords: Cutaneous malignant melanoma; Function; PDIA3; TYR; miR-330-5p.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Cell Line
  • Cell Movement
  • Cell Proliferation / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Melanoma, Cutaneous Malignant
  • MicroRNAs / metabolism*
  • Monophenol Monooxygenase / metabolism*
  • Neoplasm Invasiveness
  • Protein Disulfide-Isomerases / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • MIRN330 microRNA, human
  • MicroRNAs
  • Monophenol Monooxygenase
  • Protein Disulfide-Isomerases
  • PDIA3 protein, human