MicroRNA hsa-miR-657 promotes retinoblastoma malignancy by inhibiting peroxisome proliferator-activated receptor alpha expression

Anticancer Drugs. 2022 Jun 1;33(5):478-488. doi: 10.1097/CAD.0000000000001308.

Abstract

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.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Heterografts
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • Retinal Neoplasms* / genetics
  • Retinoblastoma* / genetics
  • Retinoblastoma* / metabolism
  • Retinoblastoma* / pathology

Substances

  • MIRN657 microRNA, human
  • MicroRNAs
  • PPAR alpha
  • PPARA protein, human