Gao Ge, Zhang Yang, Chao Yingjiu, Niu Chaoshi, Fu Xianming, Wei Jianjun
Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P.R. China.
Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui, P.R. China.
J Cell Biochem. 2019 Dec;120(12):19432-19441. doi: 10.1002/jcb.29219. Epub 2019 Sep 9.
Intracranial aneurysm (IA) is recognized as a lethal form of cerebrovascular disease mainly featured with a modulated phenotype of vascular smooth muscle cells (SMCs). It is generally believed that enhanced SMC proliferation and migration capabilities are the main characteristics in this process. In this study, we revealed that microRNA-4735 (miR-4735) participates in phenotypic modulation in a hypoxia-inducible factor-1 (HIF-1)-dependent manner of SMCs. miR-4735 targets the 3'-untranslated region of HIF-1. The downregulated expression of miR-4735 in IA tissues leads to elevated expression of HIF-1, which activates autophagy and promotes autophagy-mediated SMC proliferation and migration. Overexpression of miR-4735 suppressed HIF-1 expression and HIF-1-mediated autophagy, which led to impaired SMC proliferation and migration abilities. Forced expression of HIF-1 in miR-4735-overexpressed SMCs rescued the impaired SMC proliferation and migration abilities. In conclusion, miR-4735 plays an important role in phenotypic modulation in IA by regulating autophagy-promoted SMC proliferation and migration.
颅内动脉瘤（IA）被认为是一种致命的脑血管疾病形式，主要特征是血管平滑肌细胞（SMC）具有一种调节后的表型。一般认为，SMC增殖和迁移能力增强是这一过程的主要特征。在本研究中，我们发现微小RNA-4735（miR-4735）以缺氧诱导因子-1（HIF-1）依赖的方式参与SMC的表型调节。miR-4735靶向HIF-1的3'-非翻译区。IA组织中miR-4735表达下调导致HIF-1表达升高，激活自噬并促进自噬介导的SMC增殖和迁移。miR-4735过表达抑制HIF-1表达和HIF-1介导的自噬，导致SMC增殖和迁移能力受损。在miR-4735过表达的SMC中强制表达HIF-1挽救了受损的SMC增殖和迁移能力。总之，miR-4735通过调节自噬促进的SMC增殖和迁移在IA的表型调节中起重要作用。
