Hsa_circ_0024093 accelerates VSMC proliferation via miR-4677-3p/miR-889-3p/USP9X/YAP1 axis in in vitro model of lower extremity ASO

Arteriosclerosis obliterans (ASO) of the lower extremities is identified as a kind of cardiovascular disease with aberrant proliferation and apoptosis of vascular smooth muscle cells (VSMCs). Accumulating studies have demonstrated the vital role of Yes1-associated transcriptional regulator (YAP1) in...

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Main Authors: Xue Zhang (Author), Peng Wang (Author), Kai Yuan (Author), Maoran Li (Author), Yiting Shen (Author), Huafa Que (Author), Yunfei Wang (Author), Wei Liang (Author)
Format: Book
Published: Elsevier, 2021-12-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Xue Zhang  |e author 
700 1 0 |a Peng Wang  |e author 
700 1 0 |a Kai Yuan  |e author 
700 1 0 |a Maoran Li  |e author 
700 1 0 |a Yiting Shen  |e author 
700 1 0 |a Huafa Que  |e author 
700 1 0 |a Yunfei Wang  |e author 
700 1 0 |a Wei Liang  |e author 
245 0 0 |a Hsa_circ_0024093 accelerates VSMC proliferation via miR-4677-3p/miR-889-3p/USP9X/YAP1 axis in in vitro model of lower extremity ASO 
260 |b Elsevier,   |c 2021-12-01T00:00:00Z. 
500 |a 2162-2531 
500 |a 10.1016/j.omtn.2021.07.026 
520 |a Arteriosclerosis obliterans (ASO) of the lower extremities is identified as a kind of cardiovascular disease with aberrant proliferation and apoptosis of vascular smooth muscle cells (VSMCs). Accumulating studies have demonstrated the vital role of Yes1-associated transcriptional regulator (YAP1) in VSMCs, while its upstream regulatory mechanism in VSMCs in ASO of the lower extremities needs to be further elucidated. Herein, hsa_circ_0024093, a circular RNA (circRNA) from YAP1, was identified to positively regulate the protein level of YAP1 in VSMCs. Functionally, silencing of hsa_circ_0024093 obviously impeded cell proliferation and migration and promoted apoptosis in VSMCs in the in vitro model of ASO of the lower extremities. Mechanistically, it was found that hsa_circ_0024093 could regulate the expression of USP9X, which further induced YAP1 deubiquitination to stabilize YAP1 protein. In depth, it was revealed from mechanism experiments that hsa_circ_0024093 sequestered miR-889-3p or miR-4677-3p to enhance USP9X expression. Further, rescue assays validated that hsa_circ_0024093 regulated the miR-4677-3p/miR-889-3p/USP9X axis to accelerate the proliferation and migration of VSMCs in the in vitro model of ASO of the lower extremities. These findings may provide a novel perspective for better understanding of ASO of the lower extremities. 
546 |a EN 
690 |a arteriosclerosis obliterans 
690 |a lower extremities 
690 |a vascular smooth muscle cells 
690 |a hsa_circ_0024093 
690 |a YAP1 
690 |a USP9X 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Molecular Therapy: Nucleic Acids, Vol 26, Iss , Pp 511-522 (2021) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S2162253121001943 
787 0 |n https://doaj.org/toc/2162-2531 
856 4 1 |u https://doaj.org/article/e92f3106592d4e27b7f95b51eab9f729  |z Connect to this object online.