A Novel Mechanism of Sigma 1 Receptor Neuroprotection: Modulation of miR-214-3p

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Retinitis pigmentosa (RP) is a blinding disease for which there is no known cure. In a recent study, we reported dramatic rescue of cones in the rd10 mouse model of RP when mice were treated systemically with (+)-pentazocine ((+)-PTZ), a high-affinity ligand for sigma 1 receptor (Sig1R). The molecular mechanisms by which Sig1R provides neuroprotection are unclear. In this report, we used a miRNA PCR array to compare 84 abundantly expressed, well-characterized miRNAs in rd10/Sig1R−/− vs. rd10 and rd10 + PTZ vs. rd10 mice. We found that 13 miRNAs were significantly increased in rd10/Sig1R−/− retinas but were significantly decreased in rd10 + PTZ retinas. The miRNAs were miR-9-5p, miR-27a-3p, miR-126a-5p, miR-146a-5p, miR-10a-5p, miR-34c-5p, miR-503-5p, miR-30c-5p, miR-199-5p, miR-541-5p, miR-214-3p, miR-218-5p, and miR-335-5p. Of these, miR-214-3p is closely related to oxidative stress modulation, which is relevant to degenerative retinopathy. MiR-214-3p expression is ~fivefold higher in rd10/Sig1R−/− vs. rd10. In contrast, miR-214-3p is decreased ~twofold in rd10 + PTZ vs. rd10. Interestingly, miR-214-3p is predicted to bind to Sig1R and Nrf2, a key transcription factor for modulation of oxidative stress. To our knowledge, this is the first evidence that Sig1R may interact with miRNAs in retina. This observation is the underpinning of our hypothesis that a novel mechanism by which Sig1R mediates cone rescue is via interaction with miR-214-3p.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer
Pages463-467
Number of pages5
DOIs
StatePublished - Jan 1 2019

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1185
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Cone photoreceptor cells
  • MicroRNA
  • miR-214-3p
  • Neuroprotection
  • Nrf2
  • Oxidative stress
  • Retinal degeneration
  • Retinitis pigmentosa
  • Sigma 1 receptor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Wang, J., & Smith, S. B. (2019). A Novel Mechanism of Sigma 1 Receptor Neuroprotection: Modulation of miR-214-3p. In Advances in Experimental Medicine and Biology (pp. 463-467). (Advances in Experimental Medicine and Biology; Vol. 1185). Springer. https://doi.org/10.1007/978-3-030-27378-1_76