miR-15a: a potential diagnostic biomarker and a candidate for non-operative therapeutic modality for age-related cataract

Br J Biomed Sci. 2019 Oct;76(4):184-189. doi: 10.1080/09674845.2019.1639337. Epub 2019 Aug 14.

Abstract

Introduction: In order to better understand the role of hsa-miR-15a in the pathogenesis of age-related cataracts, we hypothesised altered expression, and of target anti-apoptotic genes, BCL-2 and MCL-1, in lens epithelial cells amongst age-related cataract patients.Material and methods: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) quantified the expression of hsa-miR-15a and the target genes BCL-2 and MCL-1 in lens epithelial cells of 120 age-related cataract patients (40 patients with cortical cataracts, 40 patients with nuclear cataracts and 40 patients with posterior subcapsular cataracts) and 40 controls. Sixty specimens (15 normal and 45 cataracts) were stained immunohistochemically with BCL-2 and MCL-1 markers.Results: The expression of hsa-miR-15a was significantly increased (p = 0.003) in lens epithelial cells of cataract patients compared to the control group. BCL-2 and MCL-1 expression levels were significantly decreased in cataract patients (p < 0.001). A significant increase in hsa-miR-15a expression in the cortical subtype compared to the posterior subcapsular subtype (p = 0.003) and a significant decrease in BCL-2 and MCL-1 expressions in the cortical subtype compared to the nuclear and the posterior subcapsular subtype was detected.Conclusions: The increased expression of hsa-miR-15a in lens epithelial cells of cataract patients may repress the expression of BCL-2 and MCL-1. The expression of hsa-miR-15a and the subsequent apoptosis of lens epithelial cells are part of the pathogenesis of age-related cataracts.

Keywords: Age-related cataract; BCL-2; MCL-1; apoptosis; hsa-miR-15a.

MeSH terms

  • Aging / genetics*
  • Apoptosis / genetics
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cataract / classification
  • Cataract / diagnosis*
  • Cataract / genetics
  • Cataract / pathology
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Gene Expression Regulation
  • Humans
  • Lens, Crystalline / metabolism
  • Lens, Crystalline / pathology
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics*
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism

Substances

  • BCL2 protein, human
  • Biomarkers
  • MCL1 protein, human
  • MIRN15 microRNA, human
  • MicroRNAs
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2