LncRNA CRNDE affects the proliferation and apoptosis of vascular smooth muscle cells in abdominal aortic aneurysms by regulating the expression of Smad3 by Bcl-3

Cell Cycle. 2020 May;19(9):1036-1047. doi: 10.1080/15384101.2020.1743915. Epub 2020 Apr 2.

Abstract

Previous studies show that Long non-coding RNAs (LncRNAs) are involved in the regulation of various human diseases. This study aimed to reveal how LncRNA CRNDE regulated vascular smooth muscle cells (VSMCs) proliferation and apoptosis in abdominal aortic aneurysms (AAA). Here, we found CRNDE was down-regulated in AAA tissues and AngII-stimulated VSMCs. The overexpression of CRNDE promoted VSMCs proliferation and inhibited cell apoptosis. The interaction between CRNDE and Bcl-3 or Bcl-3 and Smad3 was verified. The interference with Bcl-3 or CRNDE reduced Smad3 stability or promoted Smad3 ubiquitination. After pcDNA-CRNDE or pcDNA-CRNDE+si-Bcl-3 was transfected into VSMCs and stimulated with AngII, CRNDE affected VSMCs proliferation and apoptosis via regulating Smad3 via Bcl-3. Vivo experiments showed the overexpression of CRNDE repressed AAA growth. Therefore, we concluded that CRNDE was down-regulated in AAA tissues and AngII-stimulated VSMCs. Furthermore, the overexpression of CRNDE promoted VSMCs proliferation and repressed cell apoptosis in AAA by up-regulating Smad3 via Bcl-3.

Keywords: AAA; Bcl-3; LncRNA CRNDE; Smad3; VSMCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aortic Aneurysm, Abdominal / genetics
  • Aortic Aneurysm, Abdominal / metabolism*
  • Aortic Aneurysm, Abdominal / pathology
  • Apoptosis / genetics*
  • B-Cell Lymphoma 3 Protein / genetics
  • B-Cell Lymphoma 3 Protein / metabolism*
  • Cell Proliferation / genetics*
  • Cells, Cultured
  • Disease Models, Animal
  • Down-Regulation
  • Genetic Vectors / administration & dosage
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE
  • Muscle, Smooth, Vascular / metabolism*
  • Myocytes, Smooth Muscle / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction / genetics*
  • Smad3 Protein / metabolism*
  • Transfection
  • Up-Regulation / genetics

Substances

  • B-Cell Lymphoma 3 Protein
  • BCL3 protein, human
  • CRNDE RNA, human
  • RNA, Long Noncoding
  • SMAD3 protein, human
  • Smad3 Protein

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant number 81301328, 2013) and Henan provincial Medical Science and technology research program (grant number 201602216, 2016).