Retinoblastoma is a familial inherited embryonic neuroretinal malignancy with a low survival rate and poor prognosis. Our study aimed to evaluate the potential interaction between microRNA miR-657 and the peroxisome proliferator-activated receptor alpha (PPARA) in retinoblastoma. Expression of miR-657 and PPARA was analyzed in retinoblastoma tissues and cells using RT-qPCR. Cell proliferation, apoptosis, and migration were measured in retinoblastoma cell lines, and xenografting experiments were performed using nude mice. Our study showed that miR-657 expression was markedly increased, whereas that of PPARA was markedly decreased in retinoblastoma. Additionally, PPARA knockdown enhanced the development of retinoblastoma. miR-657 enhanced the retinoblastoma tumorigenesis by directly inhibiting PPARA expression, suggesting that PPARA targeting by miR-657 facilitates retinoblastoma development by enhancing cell growth. This study provides novel insights into the miR-657- and PPARA-mediated mechanisms underlying retinoblastoma progression and suggests that the interaction between miR-657 and PPARA may serve as an effective target for therapeutic intervention.
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