Details

Autor(en) / Beteiligte

• Min, Xue
• Cai, Meng‐yun
• Shao, Tong
• Xu, Zi‐yang
• Liao, Zhaofu
• Liu, Dong‐liang
• Zhou, Meng‐yuan
• Wu, Wei‐peng
• Zhou, Yu‐lan
• Mo, Miao‐hua
• Xu, Shun
• Liu, Xinguang
• Xiong, Xing‐dong

Titel

A circular intronic RNA ciPVT1 delays endothelial cell senescence by regulating the miR‐24‐3p/CDK4/pRb axis

Ist Teil von

• Aging cell, 2022-01, Vol.21 (1), p.e13529-n/a

Ort / Verlag

England: John Wiley & Sons, Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Circular RNAs (circRNAs) have been established to be involved in numerous processes in the human genome, but their function in vascular aging remains largely unknown. In this study, we aimed to characterize and analyze the function of a circular intronic RNA, ciPVT1, in endothelial cell senescence. We observed significant downregulation of ciPVT1 in senescent endothelial cells. In proliferating endothelial cells, ciPVT1 knockdown induced a premature senescence‐like phenotype, inhibited proliferation, and led to an impairment in angiogenesis. An in vivo angiogenic plug assay revealed that ciPVT1 silencing significantly inhibited endothelial tube formation and decreased hemoglobin content. Conversely, overexpression of ciPVT1 in old endothelial cells delayed senescence, promoted proliferation, and increased angiogenic activity. Mechanistic studies revealed that ciPVT1 can sponge miR‐24‐3p to upregulate the expression of CDK4, resulting in enhanced Rb phosphorylation. Moreover, enforced expression of ciPVT1 reversed the senescence induction effect of miR‐24‐3p in endothelial cells. In summary, the present study reveals a pivotal role for ciPVT1 in regulating endothelial cell senescence and may have important implications in the search of strategies to counteract the development of age‐associated vascular pathologies. We characterized a novel circular intronic RNA ciPVT1, which originates from intron 4 of the PVT1 gene, was markedly reduced in senescent endothelial cells. Further functional and mechanistic investigations revealed that ciPVT1 may act as a competing endogenous RNA (ceRNA) to regulate CDK4 and its downstream gene by decoying miR‐24‐3p, thereby delaying endothelial cell senescence.