MicroRNA-329 upregulation impairs the HMGB2/β-catenin pathway and regulates cell biological behaviors in melanoma

J Cell Physiol. 2019 Dec;234(12):23518-23527. doi: 10.1002/jcp.28920. Epub 2019 Jun 20.

Abstract

Melanoma is responsible for the majority of deaths caused by skin cancer. Antitumor activity of microRNA-329 (miR-329) has been seen in several human cancers. In this study, we identify whether miR-329 serves as a candidate regulator in melanoma. Melanoma-related differentially expressed genes were screened with its potential molecular mechanism predicted. Melanoma tissues and pigmented nevus tissues were collected, where the levels of miR-329 and high-mobility group box 2 (HMGB2) were determined. To characterize the regulatory role of miR-329 on HMGB2 and the β-catenin pathway in melanoma cell activities, miR-329 mimics, miR-329 inhibitors, and siRNA-HMGB2 were transfected into melanoma cells. Cell viability, migration, invasion, cell cycle, and apoptosis were assessed. miR-329 was predicted to influence melanoma by targeting HMGB2 via the β-catenin pathway. High level of HMGB2 and low miR-329 expression were observed in melanoma tissues. HMGB2 was targeted and negatively regulated by miR-329. In melanoma cells transfected with miR-329 mimics or siRNA-HMGB2, cell proliferation, migration, and invasion were impeded, yet cell cycle arrest and apoptosis were promoted, corresponding to decreased levels of β-catenin, cyclin D1, and vimentin and increased levels of GSK3β and E-cadherin. Collectively, our results show that miR-329 can suppress the melanoma progression by downregulating HMGB2 via the β-catenin pathway.

Keywords: apoptosis; high-mobility group box 2; invasion; melanoma; microRNA-329; migration; proliferation; β-catenin pathway.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Apoptosis
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • HMGB2 Protein / genetics
  • HMGB2 Protein / metabolism*
  • Humans
  • Male
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Signal Transduction
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Vimentin / genetics
  • Vimentin / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Antigens, CD
  • CCND1 protein, human
  • CDH1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • HMGB2 Protein
  • MIRN329 microRNA, human
  • MicroRNAs
  • VIM protein, human
  • Vimentin
  • beta Catenin
  • Cyclin D1
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta