miR-762 regulates the proliferation and differentiation of retinal progenitor cells by targeting NPDC1

Cell Cycle. 2020 Jul;19(14):1754-1767. doi: 10.1080/15384101.2020.1777805. Epub 2020 Jun 16.

Abstract

Retinal degenerations, which lead to irreversible decline in visual function, are still no effective recovery treatments. Currently, retinal progenitor cell (RPC) transplantation therapy is expected to provide a new approach to treat these diseases; however, the limited proliferation capacity and differentiation potential toward specific retinal neurons of RPCs hinder their potential clinical applications. microRNAs have been reported to serve as important regulators in the cell fate determination of stem/progenitor cells. In this study, our data demonstrated that miR-762 inhibited NPDC1 expression to positively regulate RPC proliferation and suppress RPC neuronal differentiation. Furthermore, the knockdown of miR-762 upregulated NPDC1 expression in RPCs, leading to the inhibition of RPC proliferation and the increase in neuronal differentiation. Moreover, NPDC1 could rescue anti-miR-762-induced RPC proliferation deficiency and the inhibitory effect of miR-762 on RPC differentiation. In conclusion, our study demonstrated that miR-762 plays a crucial role in regulating RPC proliferation and differentiation by directly targeting NPDC1, which is firstly reported that microRNAs positively regulate RPC proliferation and negatively regulate RPC differentiation, which provides a comprehensive understanding of the molecular mechanisms that dominate RPC proliferation and differentiation in vitro.

Keywords: NPDC1; Retinal progenitor cells; differentiation; miR-762; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Gene Expression Regulation
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Models, Biological
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism*
  • Retina / cytology*

Substances

  • MIRN762 microRNA, mouse
  • MicroRNAs
  • Nerve Tissue Proteins
  • Npdc1 protein, mouse

Grants and funding

The National Natural Science Foundations of China (81870687), the National Key R&D program of China (2018YFC1106100, 2018YFC1106101), the Science and Technology Commission of Shanghai (19JC1415503, 17DZ2260100), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20161316) and innovative research team of high-level local universities in Shanghai