Circular RNA circ_0079593 enhances malignant melanoma progression by the regulation of the miR-573/ABHD2 axis

J Dermatol Sci. 2021 Apr;102(1):7-15. doi: 10.1016/j.jdermsci.2021.01.008. Epub 2021 Feb 4.

Abstract

Background: Malignant melanoma is the most fatal type of skin tumor. Circular RNAs (circRNAs) have been implicated in the malignant progression of melanoma.

Objective: The main purpose of this paper was to identify the precise parts of circ_0079593 in the malignant progression of melanoma.

Methods: The levels of circ_0079593, miR-573 and abhydrolase domain containing 2 (ABHD2) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell proliferation, colony formation, cell cycle progression, apoptosis, migration, and invasion were evaluated using the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays, respectively. Targeted correlations among circ_0079593, miR-573 and ABHD2 were confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Animal studies were performed to assess the role of circ_0079593 in vivo.

Results: Our data showed that circ_0079593 level was up-regulated in melanoma tissues and cells. The knockdown of circ_0079593 suppressed cell proliferation, cell cycle progression, migration, invasion, and enhanced apoptosis in vitro and inhibited tumor growth in vivo. Mechanistically, circ_0079593 directly targeted miR-573, and circ_0079593 controlled ABHD2 expression by miR-573. MiR-573 mediated the regulation of circ_0079593 on melanoma cell progression in vitro. Moreover, ABHD2 was a functional target of miR-573 in regulating melanoma cell progression in vitro.

Conclusion: Our findings identified that the knockdown of circ_0079593 suppressed melanoma progression at least partially through targeting the miR-573/ABHD2 axis, providing evidence for developing circ_0079593 as a promising therapeutic target for melanoma treatment.

Keywords: ABHD2; Malignant progression; Melanoma; circ_0079593; miR-573.

Publication types

  • Observational Study

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Biopsy
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Healthy Volunteers
  • Humans
  • Hydrolases / genetics*
  • Male
  • Melanocytes
  • Melanoma / diagnosis
  • Melanoma / genetics*
  • Melanoma / pathology
  • Mice
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA, Small Interfering / metabolism
  • Skin / pathology
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • MIRN573 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Small Interfering
  • Hydrolases
  • ABHD2 protein, human