MicroRNA‑34b‑5p inhibits proliferation, stemness, migration and invasion of retinoblastoma cells via Notch signaling
Affiliations: Department of Ophthalmology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China
- Published online on: January 25, 2021 https://doi.org/10.3892/etm.2021.9686
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Retinoblastoma (RB) is one of the most common forms of childhood intraocular cancer. While the occurrence of RB is traditionally associated with dysregulation of the RB1 gene, efforts have been made to assess the role of several other pathways that may result in RB. The Notch signaling pathway has been identified as one of the sentinel pathways in retinal development and has been indicated to serve as a tumor suppressor. However, epigenetic modifications of the Notch signaling pathway, and their consequences on tumor establishment and progression, have received little attention. The present study attempted to elucidate the microRNA (miR)‑mediated dysregulation of the Notch signaling pathway and its implications on tumor initiation. Upon recruitment of patients with RB (age, 4‑25 months), the levels of miR‑34b‑5p were determined in tumor and adjacent healthy tissues. Simultaneously, the serum levels of miR‑34b‑5p were measured in tumor and healthy samples using reverse transcriptase‑quantitative PCR (RT‑qPCR). Binding of miR‑34b‑5p to Notch1 and Notch2 were confirmed bioinformatically. In vitro studies were performed in Y79 and Weri‑Rb‑1 RB cell lines. The cell lines were transfected with miR‑34b‑5p constructs and miR‑34b‑5p overexpression was confirmed using RT‑qPCR. The impact of miR‑34b‑5p overexpression on cell growth and cancer stemness markers (Sox‑2, Nanog, and CD133) was examined. The expression levels of Notch1 and Notch2 were evaluated in the presence of miR‑34b‑5p. The rescue of cell growth and cancer stemness phenotypes was evaluated by co‑transfection of miR‑34b‑5p with Notch1 or Notch2. The results of the present study indicated that the expression levels of miR‑34b‑5p were reduced in patient tissues and serum samples compared with those in healthy tissues and samples. Notch1 and Notch2 expression level was negatively correlated with the expression level of miR‑34b‑5p. Overexpression of miR‑34b‑5p resulted in reduced cell proliferation, migration, invasion and cancer stemness compared with the control group. Further in vivo experiments confirmed the inhibitory effects of miR‑34b‑5p on RB cell proliferation. Upon co‑transfection of miR‑34b‑5p with Notch1 or Notch2, these phenotypes were rescued with reversal of cell growth and tumor sphere formation. Collectively, the results indicated that miR‑34b‑5p functions as a tumor suppressor in RB via regulating the Notch signaling pathway. Therefore, miR‑34b‑5p may be explored for its utility as a therapeutic target in RB.