MiR-130a-3p Enhances the Chemosensitivity of Y79 Retinoblastoma Cells to Vincristine by Targeting PAX6 Expression

Abstract

ABSTRACTPurposeChemoresistance remains the primary obstacle threatening the prognosis of retinoblastoma (RB). microRNAs (miRNAs) are acknowledged as critical regulators of drug resistance. This study explored the molecular mechanism of miR-130a-3p affecting the chemosensitivity of RB to vincristine (VCR).MethodsmiR-130a-3p expression of human retinal astrocytes and RB cell lines (Y79, WERI-Rb-1, SO-Rb50, and SO-Rb70) was detected using RT-qPCR. VCR-resistant RB cell line Y79/VCR was induced. miR-130a-3p expression of Y79/VCR cell line and its corresponding parental cell line was detected. Y79/VCR cells were subjected to miR-130a-3p overexpression treatment. The cell proliferation was measured using MTT assay, and the IC50 value and drug resistance index were examined using CCK-8 assay. The targeting relationship between miR-130a-3p and PAX6 was predicted through bioinformatics analysis and verified using dual-luciferase assay. Functional rescue experiments were conducted to confirm the role of PAX6 in chemosensitivity of RB cells. The effect of miR-130a-3p on tumorigenesis and VCR sensitivity was observed in vivo.ResultsmiR-130a-3p was downregulated in VCR-resistant RB cells. Overexpression of miR-130a-3p repressed the proliferation of Y79/VCR cells and enhanced chemosensitivity. miR-130a-3p targeted PAX6 expression. Overexpression of PAX6 reversed the effect of miR-130a-3p on chemosensitivity of Y79/VCR cells. Overexpression of miR-130a-3p suppressed tumor growth and reduced VCR resistance in vivo.ConclusionsmiR-130a-3p enhanced the chemosensitivity of Y79 RB cells to VCR by targeting PAX6 expression.