Downregulation of microRNA‑182 inhibits cell viability, invasion and angiogenesis in retinoblastoma through inhibition of the PI3K/AKT pathway and CADM2 upregulation

  • Authors:
    • Yan‑Xia Huang
    • Xin‑Gang Nie
    • Guang‑Da Li
    • Dong‑Sheng Fan
    • Li‑Li Song
    • Xin‑Lin Zhang
  • View Affiliations

  • Published online on: October 9, 2018     https://doi.org/10.3892/ijo.2018.4587
  • Pages: 2615-2626
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Abstract

Retinoblastoma (RB) is a well‑vascularized tumor dependent on angiogenesis. The present study aimed to explore whether microRNA (miR)‑182 regulates cell viability, invasion and angiogenesis in RB via the phosphatidylinositol‑3‑OH kinase (PI3K)/protein kinase B (AKT) signaling pathway and by targeting cell adhesion molecule 2 (CADM2). The expression levels of miR‑182 and CADM2 were initially detected in RB tissues from patients with RB who underwent ophthalmectomy, and normal retinal tissues collected from other trauma patients who underwent eye enucleation. To determine whether CADM2 was targeted by miR‑182, a dual luciferase reporter assay was conducted. Subsequently, Y79 and WERI‑Rb‑1 RB cells were transfected with a miR‑182 mimic or miR‑182 inhibitor, or small interfering RNA against CADM2, in order to investigate the effects of miR‑182 on viability and invasion, which were detected using MTT and Transwell assays, respectively. In addition, to determine whether the regulatory mechanism underlying the effects of miR‑182 was associated with the PI3K/AKT signaling pathway, the expression levels of associated genes were detected by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. A xenograft tumor model in nude mice was also established, in order to evaluate the effects of miR‑182 on tumor growth and angiogenesis. The results indicated that miR‑182 expression was increased and CADM2 expression was reduced in RB tissues; CADM2 was confirmed to be targeted and negatively regulated by miR‑182. When the expression of miR‑182 was downregulated, cell viability, invasion, tumor volume and angiogenesis were significantly decreased. Furthermore, the expression levels of PI3K/AKT signaling pathway‑associated genes were increased in response to miR‑182 overexpression or CADM2 silencing. Taken together, these results suggested that inhibition of miR‑182 may suppress cell viability, invasion and angiogenesis in RB through inactivation of the PI3K/AKT pathway and CADM2 upregulation. This mechanism may reveal a novel potential therapeutic target.
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December-2018
Volume 53 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Huang YX, Nie XG, Li GD, Fan DS, Song LL and Zhang XL: Downregulation of microRNA‑182 inhibits cell viability, invasion and angiogenesis in retinoblastoma through inhibition of the PI3K/AKT pathway and CADM2 upregulation. Int J Oncol 53: 2615-2626, 2018.
APA
Huang, Y., Nie, X., Li, G., Fan, D., Song, L., & Zhang, X. (2018). Downregulation of microRNA‑182 inhibits cell viability, invasion and angiogenesis in retinoblastoma through inhibition of the PI3K/AKT pathway and CADM2 upregulation. International Journal of Oncology, 53, 2615-2626. https://doi.org/10.3892/ijo.2018.4587
MLA
Huang, Y., Nie, X., Li, G., Fan, D., Song, L., Zhang, X."Downregulation of microRNA‑182 inhibits cell viability, invasion and angiogenesis in retinoblastoma through inhibition of the PI3K/AKT pathway and CADM2 upregulation". International Journal of Oncology 53.6 (2018): 2615-2626.
Chicago
Huang, Y., Nie, X., Li, G., Fan, D., Song, L., Zhang, X."Downregulation of microRNA‑182 inhibits cell viability, invasion and angiogenesis in retinoblastoma through inhibition of the PI3K/AKT pathway and CADM2 upregulation". International Journal of Oncology 53, no. 6 (2018): 2615-2626. https://doi.org/10.3892/ijo.2018.4587