Hsa_circ_0024093 accelerates VSMC proliferation via miR-4677-3p/miR-889-3p/USP9X/YAP1 axis in in vitro model of lower extremity ASO
| Autor: | Peng Wang, Yiting Shen, Hua-Fa Que, Yun-fei Wang, Maoran Li, Kai Yuan, Xue Zhang, Wei Liang |
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| Rok vydání: | 2021 |
| Předmět: |
YAP1
Vascular smooth muscle lower extremities Cell growth Chemistry USP9X RM1-950 hsa_circ_0024093 Cell biology Apoptosis Circular RNA Drug Discovery Transcriptional regulation vascular smooth muscle cells Molecular Medicine Gene silencing Original Article arteriosclerosis obliterans Therapeutics. Pharmacology |
| Zdroj: | Molecular Therapy: Nucleic Acids, Vol 26, Iss, Pp 511-522 (2021) Molecular Therapy. Nucleic Acids |
| ISSN: | 2162-2531 |
| DOI: | 10.1016/j.omtn.2021.07.026 |
| Popis: | 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. Graphical abstract It was revealed that hsa_circ_0024093 regulated the miR-4677-3p/miR-889-3p/USP9X axis to promote YAP1 deubiquitination and enhance YAP1 protein stability, finally accelerating VSMC proliferation and migration in arteriosclerosis obliterans of the lower extremities. This may provide a novel understanding of arteriosclerosis obliterans of the lower extremities. |
| Databáze: | OpenAIRE |
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