Knockdown of circ_0084043 suppresses the development of human melanoma cells through miR-429/tribbles homolog 2 axis and Wnt/β-catenin pathway

Aims: Circular RNAs (circRNAs) have been emerged as novel regulators in multiple tumorigenesis, including melanoma. CircRNA_0084043 was recently demonstrated to be deregulated in human melanoma cells. Nevertheless, its role and mechanism are largely unrevealed in melanoma. Materials and methods: Expression of circ_0084043, miRNA (miR)-429 and tribbles homolog 2 (TRIB2) was detected using reverse transcription-quantitative PCR quantitative PCR (RT-qPCR) and western blotting. Cell proliferation, apoptosis, migration and invasion were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and transwell assays, respectively. The activation of Wnt/beta-catenin pathway was evaluated by western blotting. The target binding among circ_0084043, miR-429 and TRIB2 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation. In vivo, mice xenograft model was generated to investigate tumor growth. Key findings: Expression of circ_0084043 and TRIB2 was upregulated in human melanoma tissues and cell lines. Both circ_0084043 knockdown and TRIB2 silencing could decrease cell proliferation, migration and invasion, but facilitate apoptosis in A375 and SK-MEL-28 cells. Furthermore, TRIB2 restoration partially abrogated the tumor-suppressive role of circ_0084043 knockdown in melanoma cells in vitro. Then, we verified that circ_0084043 positively and physically controlled TRIB2 expression through sponging miR-429. Besides, expression of beta-catenin, c-Myc and cyclinD1 was inhibited in A375 and SK-MEL-28 cells when circ_0084043 was knocked down, accompanied with increased miR-429 and decreased TRIB2. Notably, circ_0084043 downregulation impeded tumor growth of A375 cells in vivo. Significance: Knockdown of circ_0084043 suppressed the malignant development of melanoma presumably through modulating miR429/TRIB2 axis and inactivating Wnt/beta-catenin signaling pathway.