Journal
BIOCHEMISTRY AND CELL BIOLOGY
Volume 97, Issue 5, Pages 571-580Publisher
CANADIAN SCIENCE PUBLISHING
DOI: 10.1139/bcb-2018-0126
Keywords
lncRNA-ANRIL; cellular senescence; miR-181a; Sirt1; vascular smooth muscle cells
Categories
Funding
- Youth Project of Hunan Provincial Natural Science Foundation [2018JJ3768]
- Youth Science Project of National Natural Science Foundation of China [81501212]
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Background: Cardiovascular disease is one of the major threats to human life and health, and vascular aging is an important cause of its occurrence. Antisense non-coding RNA in the INK4 locus (ANRIL) is a kind of long non-coding RNA (lncRNA) that plays important roles in cell senescence. However, the role and mechanism of ANRIL in senescence of vascular smooth muscle cells (VSMCs) are unclear. Methods: Cell viability and cell cycle were evaluated using an MTT assay and flow cytometry analysis, respectively. Senescence-associated (SA)-beta-galactosidase (gal) staining was used to determine cell senescence. Dual luciferase reporter assays were conducted to confirm the binding of ANRIL and miR-181a, as well as miR-181a and Sirt1. The expression of ANRIL, miR-181a, and Sirt1 was determined using qRT-PCR and protein levels of SA-beta-gal and p53-p21 pathway-related proteins were evaluated by Western blotting. Results: ANRIL and Sirt1 were down-regulated, whereas miR-181a was up-regulated in aging VSMCs. In young and aging VSMCs, over-expression of ANRIL could down-regulate miR-181a and up-regulate Sirt1. MTT and SA-beta-gal staining assays showed that over-expression of ANRIL and inhibition of miR-181a promoted cell viability and inhibited VSMC senescence. The dual-luciferase reporter assay determined that miR-181a directly targets ANRIL and the 3'-UTR of Sirt1. Furthermore, over-expression of ANRIL inhibited cell cycle arrest and the p53-p21 pathway. Conclusion: ANRIL promotes cell viability and inhibits senescence in VSMCs, possibly by regulating miR-181a/Sirt1, and alleviating cell cycle arrest by inhibiting the p53-p21 pathway. This study provides novel insights for the role of ANRIL in the development of cell senescence.
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