Hsa_circ_0001304 promotes vascular neointimal hyperplasia accompanied by autophagy activation

作者：Shiqing Mu, Jiajie Lin, Yu Wang, Liyun Yang, Sen Wang, Zhaoyi Wang, Anqi Zhao, Wenjun Luo, Zi-Qi Dong, Yuguang Cao, Ze-An Jiang, Sifan Wang, Shan‐Hu Cao, Meng Li, Li Yang, Shuyan Yang, Shao-Guang Sun · 发表于：Communications Biology · 年份：2025 · DOI：10.1038/s42003-025-07580-4 · 被引用次数：5 · 研究领域：Circular RNAs in diseases、Cancer-related molecular mechanisms research、Galectins and Cancer Biology

Aberrant autophagy in vascular smooth muscle cells (VSMCs) is associated with the progression of vascular remodeling diseases caused by neointimal hyperplasia. Platelet-derived growth factor-BB (PDGF-BB)-induced vascular remodeling is accompanied by autophagy activation, however, the involvement of circular RNAs (circRNAs) remains unclear. Here, we show the role of PDGF-BB-regulated hsa_circ_0001304 (circ-1304) in neointimal hyperplasia and its potential involvement in VSMC autophagy, while also elucidating the potential mechanisms. Functionally, overexpression of circ-1304 promotes VSMC autophagy in vitro and exacerbates neointimal hyperplasia in vivo, and this exacerbation is accompanied by autophagy activation. Mechanistically, circ-1304 acts as a sponge for miR-636, resulting in increased protein levels of YTHDF2. Subsequently, the YTHDF2 protein promotes the degradation of mTOR mRNA by binding to the latter's m6A modification sites. We demonstrate that PDGF-BB activates VSMC autophagy via circRNA regulation. Therefore, circ-1304 may serve as a potential therapeutic target for vascular remodeling diseases.