Autophagy-related gene 7 deficiency caused by miR-154-5p overexpression suppresses the cell viability and tumorigenesis of retinoblastoma by increasing cell apoptosis

Background: Retinoblastoma is a rare cancer of the retina that accounts for 3% of all childhood cancers. The aim of this study was to illuminate the oncogenic role and potential molecular mechanisms of the microRNA miR-154-5p and autophagy-related gene 7 (ATG7) in retinoblastoma, and to establish a nude mouse model in order to explore new therapeutic horizons for the disease. Methods: Quantitative reverse transcription-polymerase chain reaction and western blot were performed to detect the expression levels of miR-154-5p and ATG7. The targeting relationship between miR-154-5p and ATG7 was analyzed by employing the luciferase reporter assay. MiR-154-5p mimic and pcDNA-ATG7 were transfected, either alone or in combination, into Y79 cells. The subsequent in vitro experiments involved four groups: the control group, miR-154-5p group, ATG7 group, and miR-154-5p + ATG7 group. Orthotopic xenograft models were established by injecting BALB/c athymic nude mice with treated and untreated Y79 cells. Results: Y79 cells were transfected with miR-NC or miR-154-5p. Compared to those in the control group, the mRNA expression levels of miR-154-5p were increased in the miR-154-5p mimic group; in contrast, decreases were observed in the mRNA and protein expression levels of ATG7. Y79 cells were transfected with PcDNA or pcDNA-ATG7. The mRNA expression level of ATG7 was increased in pcDNA-ATG7 group. MiR-154-5p was found to have an element complementary to the three prime untranslated region of ATG7. Overexpression of miR-154-5p inhibited Y79 cells proliferation and migration, and promoted Y79 cells apoptosis via targeting of ATG7. In the in vivo experiment, the tumors of the miR-154-5p group of mice were significantly reduced in weight. Tumor growth and the protein levels of Survivin were both suppressed when miR-154-5p was overexpressed in vivo; however, cell apoptosis and the protein levels of p21 were promoted. In the miR-154-5p group, the expression levels of miR-154-5p were upregulated compared to those in the control group, but the ATG7 expression level was downregulated. Conclusions: MiR-154-5p overexpression downregulated ATG7, which inhibited cell proliferation and apoptosis in vitro, as well as tumor formation in vivo.