MiR-340/iASPP axis affects UVB-mediated retinal pigment epithelium (RPE) cell damage

J Photochem Photobiol B. 2018 Sep:186:9-16. doi: 10.1016/j.jphotobiol.2018.04.005. Epub 2018 Apr 6.

Abstract

Long-term exposure to ultraviolet B (UVB) light increases the risk of UVB damage due to increased UVB absorption by the retina and may further lead to age-related eye diseases. The retinal pigment epithelium (RPE) cell is a main target of UVB reaching the retina; its degeneration is an essential event in UVB-mediated age-related macular degeneration (AMD). Herein, we first evaluated the expression and effect of iASPP, an inhibitory regulator of apoptosis, in UVB-induced RPE cell damage. Through the mechanism of RNA interference at the post-transcriptional level, miRNA affects a variety of cellular processes, including UVB-mediated cell damage. We next screened for upstream candidate miRNAs that may regulate iASPP expression. Among 8 candidate miRNAs, UVB significantly increased miR-340 levels. We also confirmed the direct binding of miR-340 to the 3'UTR of iASPP, and assessed the combined effect of miR-340 and iASPP on UVB-induced RPE cell damage. Taken together, we demonstrated the possible mechanisms involved in UVB-induced retinal damage. In RPE cells, UVB irradiation inhibits iASPP expression through inducing miR-340 expression, thereby promoting RPE cell apoptosis and suppressing cell viability via affecting p53, p21 and caspase-3 protein expression. Targeting miR-340 to rescue iASPP expression in RPE cells may help treat UVB-mediated retinal damage.

Keywords: Apoptosis; Light damage; Retinal pigment epithelium (RPE) cell; Ultraviolet B (UVB); iASPP; miR-340.

MeSH terms

  • 3' Untranslated Regions
  • Antagomirs / metabolism
  • Apoptosis / radiation effects
  • Base Sequence
  • Binding Sites
  • Caspase 3 / metabolism
  • Cell Line
  • Cell Survival / radiation effects
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Gene Expression / radiation effects
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigment Epithelium / radiation effects
  • Sequence Alignment
  • Tumor Suppressor Protein p53 / metabolism
  • Ultraviolet Rays*

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • Cyclin-Dependent Kinase Inhibitor p21
  • Intracellular Signaling Peptides and Proteins
  • MIRN340 microRNA, human
  • MicroRNAs
  • PPP1R13L protein, human
  • RNA, Small Interfering
  • Repressor Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Caspase 3