Inhibition of microRNA‑492 attenuates cell proliferation and invasion in retinoblastoma via directly targeting LATS2

Mol Med Rep. 2019 Mar;19(3):1965-1971. doi: 10.3892/mmr.2018.9784. Epub 2018 Dec 20.

Abstract

Numerous studies have demonstrated that microRNAs (miRNAs) are upregulated or downregulated in retinoblastoma (RB), and that this phenomenon is associated with the modulation of various malignant behaviours during RB occurrence and development. Therefore, the mechanisms that associate deregulated miRNAs with RB initiation and progression must be understood to identify effective therapeutic techniques for patients with RB. In the present study, miR‑492 expression was upregulated in RB tissues and cell lines. The effects of miR‑492 inhibition on the proliferation and invasion of RB cells were examined using Cell Counting kit‑8 and invasion assays. The results revealed that miR‑492 downregulation significantly decreased the proliferation and invasion of RB cells. Bioinformatics analysis predicted that large tumour‑suppressor kinase 2 (LATS2) was a putative target of miR‑492. Luciferase reporter assay, reverse transcription‑quantitative polymerase chain reaction and western blot analysis demonstrated that LATS2 was a direct target gene of miR‑492 in RB cells. In addition, LATS2 expression was downregulated in RB tissues, and its downregulation was inversely correlated with miR‑492 level. Furthermore, LATS2‑knockdown abrogated the effects of miR‑492 downregulation in RB cells. In conclusion, miR‑492 inhibition may impede the malignant behaviour of RB by directly targeting LATS2. Therefore, targeting this miRNA may be an effective therapeutic method for treating patients with RB.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / genetics*
  • Retinoblastoma / genetics*
  • Retinoblastoma / pathology
  • Signal Transduction / genetics
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics*

Substances

  • MIRN492 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Proteins
  • LATS2 protein, human
  • Protein Serine-Threonine Kinases