miR‑590‑5p inhibits tumor growth in malignant melanoma by suppressing YAP1 expression

Oncol Rep. 2018 Oct;40(4):2056-2066. doi: 10.3892/or.2018.6633. Epub 2018 Aug 7.

Abstract

The microRNAs (miRNAs/miRs) involved in the carcinogenesis and progression of malignant melanoma (MM) remain unclear. In the present study, miR‑590‑5p was identified to be upregulated in MM cells compared with human melanocytes using a reverse transcription‑quantitative polymerase chain reaction to screen established oncogenic and tumor suppressor miRNAs. miR‑590‑5p was demonstrated to inhibit the cell proliferation and tumor growth of MM cells in vitro and in vivo by performing Cell Counting Kit‑8 and tumour xenograft assays, respectively. In addition, flowcytometry assays indicated that miR‑590‑5p induced cell apoptosis and cell cycle arrest at the G1 stage in MM cells. Finally, luciferase assays and western blot analysis results confirmed that the transcriptional regulator Yes‑associated protein 1 (YAP1) is upregulated and inversely associated with miR‑590‑5p expression in MM cells, and is the direct target and functional mediator of miR‑590‑5p in MM. Altogether these results reveal the functional and mechanistic link between miR‑590‑5p and YAP1 in the progression of MM. Therefore, miR‑590‑5p is a potential therapeutic target in MM.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apoptosis*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Transcription Factors
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • MIRN590 microRNA, human
  • MicroRNAs
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human