Induction of miR-3648 Upon ER Stress and Its Regulatory Role in Cell Proliferation

Int J Mol Sci. 2017 Jun 29;18(7):1375. doi: 10.3390/ijms18071375.

Abstract

MicroRNAs (miRNAs) play important roles under multiple cellular conditions including endoplasmic reticulum (ER) stress. We found that miR-3648, a human specific microRNA, was induced under ER stress. Moreover, Adenomatous polyposis coli 2 (APC2), a tumor suppressor and a negative regulator of Wnt signaling, was found to be the direct target of miR-3648. Levels of APC2 were downregulated when cells were under ER stress or after overexpressing miR-3648. Inhibition of miR-3648 by antagomir increased APC2 levels and decreased cell proliferation. Conversely, when miR-3648 was overexpressed, APC2 levels were decreased and the cell growth increased. Our data demonstrated that ER stress mediated induction of miR-3648 in human cells, which then downregulated APC2 to increase cell proliferation.

Keywords: Adenomatous polyposis coli 2; Wnt; endoplasmic reticulum stress; miR-3648; proliferation.

MeSH terms

  • Base Sequence
  • Cell Cycle / drug effects
  • Cell Proliferation / genetics
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Down-Regulation
  • Endoplasmic Reticulum Stress / physiology*
  • Gene Expression Regulation
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • MicroRNAs / metabolism*
  • Wnt Signaling Pathway

Substances

  • APC2 protein, human
  • Cytoskeletal Proteins
  • MicroRNAs