Green tea polyphenols inhibit malignant melanoma progression via regulating circ_MITF/miR-30e-3p/HDAC2 axis

Biotechnol Appl Biochem. 2022 Apr;69(2):808-821. doi: 10.1002/bab.2153. Epub 2021 Jul 22.

Abstract

Green tea polyphenols (GTPs) are regarded as anticancer substances and have been revealed to play significant roles in the development of malignant melanoma. However, the mechanisms by which GTPs perform anticarcinogenic activity are not well elucidated. Cellular function assays revealed that GTPs inhibited melanoma cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted apoptosis in vitro. Circ_MITF expression was elevated in melanoma tissues and cells but was decreased by GTPs in cells. Functional experiments indicated circ_MITF overexpression reversed the anticancer effects of GTPs on melanoma cells. Then the underlying mechanism analysis suggested that circ_MITF served as a sponge for miR-30e-3p to upregulate the level of HDAC2. MiR-30e-3p reexpression attenuated the regulatory effects of circ_MITF on GTPs-treated melanoma cells. Silencing of miR-30e-3p promoted the malignant phenotypes in GTPs-treated melanoma cells, which were reversed by HDAC2 knockdown. Preclinically, administration of GTPs suppressed the expression of downstream target genes and repressed tumorigenesis of xenografts in nude mice. In all, GTPs suppressed melanoma progression by regulating circ_MITF/miR-30e-3p/HDAC2 axis, providing a potential therapeutic strategy for human malignant melanoma intervention.

Keywords: GTPs; HDAC2; circ_MITF; malignant melanoma; miR-30e-3p.

MeSH terms

  • Animals
  • Cell Proliferation / genetics
  • Histone Deacetylase 2 / genetics
  • Humans
  • Melanoma* / drug therapy
  • Melanoma, Cutaneous Malignant
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Microphthalmia-Associated Transcription Factor
  • Polyphenols / pharmacology
  • RNA, Circular
  • Skin Neoplasms
  • Tea

Substances

  • MITF protein, human
  • MicroRNAs
  • Microphthalmia-Associated Transcription Factor
  • Polyphenols
  • RNA, Circular
  • Tea
  • HDAC2 protein, human
  • Hdac2 protein, mouse
  • Histone Deacetylase 2