miR-22-Mediated Regulation of Wnt/β-Catenin Signaling by Curcumin in Retinoblastoma.

Abstract

Retinoblastoma (RB) is a common intraocular malignant tumor affecting infants and children, yet its precise etiology and pathogenesis remain incompletely understood. Curcumin, a bioactive polyphenol, inhibits tumor progression via microRNA-mediated modulation of the Wnt/β-catenin signaling cascade. This study aimed to clarify how curcumin mediates its antitumor effects in RB by investigating its regulation of miRNA-22 (miR-22) expression and exploring the underlying molecular mechanisms. Two validated retinoblastoma models (SO-RB50/WERI-Rb-1) were treated with curcumin at varying concentrations. To delineate miR-22's regulation of Wnt/β-catenin signaling, target cells were transduced with either a miR-22 mimic lentivirus or a non-functional control lentivirus. Xenograft tumor models were established in mice using human RB cells to observe the in vivo effects of curcumin on tumor size, miR-22 expression, and Wnt/β-catenin protein levels. Cellular proliferation, invasion, and apoptosis were assessed using the CCK-8, Transwell, and Annexin V-APC-PI dual staining assay, respectively. miR-22 levels were quantified by RT-PCR, and Wnt1 and β-catenin expression profiles were determined by Western blot analysis. Curcumin treatment resulted in decreased proliferation and invasiveness in RB cells, while enhancing apoptosis and elevating miR-22 expression. Inhibition of miR-22 diminished curcumin's effects on the Wnt/β-catenin signaling pathway. In xenograft studies, curcumin significantly reduced tumor size and enhanced miR-22 expression within the tumors, effectively suppressing Wnt/β-catenin signaling. These findings demonstrate that curcumin inhibits RB cell proliferation and invasiveness while promoting apoptosis, primarily mediated through miR-22 upregulation and subsequent inhibition of the Wnt/β-catenin pathway.