AGAP2-AS1/BRD7/c-Myc signaling axis promotes skin cutaneous melanoma progression.

OBJECTIVE

To examine the effects and mechanisms of AGAP2 Antisense RNA 1 (AGAP2-AS1) in progression of skin cutaneous melanoma (SKCM).

METHODS

AGAP2-AS1 expression and SKCM survival outcomes were assessed using bioinformatics analysis. In vitro and in vivo assays, including cell proliferation, colony formation, migration, and tumor formation assays, were performed to detect AGAP2-AS1 oncogenic effects in SKCM. RNA pull-down, RNA immunoprecipitation (RIP), and co-immunoprecipitation were used to evaluate the mechanism of AGAP2-AS1 in SKCM progression.

RESULTS

AGAP2-AS1 was upregulated in human SKCM tissues and cells and predicted a worse prognosis. AGAP2-AS1 silencing in two SKCM cell lines inhibited cell proliferation, as well as colony formation and migration both in vitro and in vivo. The RNA pull-down assay and RIP analysis results indicated that AGAP2-AS1 interacted with bromodomain containing 7 (BRD7). AGAP2-AS1 knockdown attenuated the BRD7 and c-Myc interaction, which reduced c-Myc expression. The altered phenotypes found in AGAP2-AS1- and BRD7-deficient cells were rescued by overexpression of c-Myc.

CONCLUSIONS

AGAP2-AS1 participated in oncogenesis in SKCM via the BRD7/c-Myc signaling pathway. These results suggest a molecular mechanism for AGAP2-AS1 in the carcinogenesis of SKCM.