Circ_0062270 upregulates EPHA2 to facilitate melanoma progression via sponging miR-331-3p

J Dermatol Sci. 2021 Sep;103(3):176-182. doi: 10.1016/j.jdermsci.2021.08.005. Epub 2021 Aug 19.

Abstract

Background: Circular RNA (circRNA) has been confirmed to play a vital role in melanoma progression.

Objective: The regulatory function of circ_0062270, a novel circRNA, in melanoma progression is unclear.

Methods: Relative expression levels of circ_0062270 and microRNA (miR)-331-3p were determined using qRT-PCR. Cell counting kit 8 assay, EdU staining and flow cytometry were used to measure cell proliferation, cell cycle distribution and apoptosis. The protein levels of proliferation, apoptosis and metastasis-related markers, as well as EPH receptor A2 (EPHA2), were tested using western blot analysis. Besides, cell migration and invasion were evaluated using transwell assay. Meanwhile, the interaction between miR-331-3p and circ_0062270 or EPHA2 was confirmed by dual-luciferase reporter assay or RIP assay. Additionally, tumor xenograft models were constructed to investigate the function of circ_0062270 on melanoma tumor growth in vivo.

Results: The expression of circ_0062270 was increased in melanoma tissues and cells. Knockdown of circ_0062270 inhibited proliferation, promoted apoptosis, and repressed metastasis in melanoma. Moreover, circ_0062270 could serve as miR-331-3p sponge, and miR-331-3p could target EPHA2. Furthermore, miR-331-3p inhibitor and EPHA2 overexpression reversed the inhibitory effect of circ_0062270 silencing on melanoma progression. In addition, silenced circ_0062270 also could inhibit melanoma tumor growth in vivo.

Conclusion: Circ_0062270 accelerated the progression of melanoma through regulating the miR-331-3p/EPHA2 axis, suggesting that circ_0062270 might be a novel potential therapeutic target for melanoma.

Keywords: EPHA2; Melanoma; circ_0062270; miR-331-3p.

Publication types

  • Observational Study

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Melanoma / diagnosis
  • Melanoma / genetics*
  • Melanoma / pathology
  • Melanoma / surgery
  • Mice
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Receptor, EphA2 / genetics*
  • Skin / pathology
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / surgery
  • Xenograft Model Antitumor Assays

Substances

  • EPHA2 protein, human
  • MIRN331 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Receptor, EphA2