Inhibition of tiRNA-Gly-GCC ameliorates neointimal formation via CBX3-mediated VSMCs phenotypic switching

Zhihua Rong; Fengshi Li; Rui Zhang; Shuai Niu; Xiao Di; Leng Ni; Changwei Liu

doi:10.3389/fcvm.2023.1030635

Inhibition of tiRNA-Gly-GCC ameliorates neointimal formation via CBX3-mediated VSMCs phenotypic switching

Front Cardiovasc Med. 2023 Feb 3:10:1030635. doi: 10.3389/fcvm.2023.1030635. eCollection 2023.

Authors

Zhihua Rong¹, Fengshi Li¹, Rui Zhang¹, Shuai Niu¹, Xiao Di¹, Leng Ni¹, Changwei Liu¹

Affiliation

¹ Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract

Background and aim: tRNA-derived fragments (tRFs) are a new class of non-coding RNAs involved in a variety of pathological processes, but their biological functions and mechanisms in human aortic smooth muscle cells (HASMCs) phenotype transition and vascular intimal hyperplasia are unclear.

Methods/results: tiRNA-Gly-GCC is upregulated in synthetic HASMCs, atherosclerotic arteries, plasma, and the balloon injured carotid artery of rats. Functionally, the inhibition of tiRNA-Gly-GCC represses HASMCs proliferation, migration, and reversed dedifferentiation, whereas the overexpression of tiRNA- Gly-GCC have contrary effects. Mechanistically, tiRNA-Gly-GCC performs these functions on HASMCs via downregulating chromobox protein homolog 3 (CBX3). Finally, the inhibition of tiRNA-Gly-GCC could ameliorate neointimal formation after vascular injury in vivo.

Conclusions: tiRNA-Gly-GCC is a mediator of HASMCs phenotypic switching by targeting CBX3 and inhibition of tiRNA-Gly-GCC suppresses neointimal formation.

Keywords: VSMC; neointimal formation; phenotypic switching; tRFs; tiRNA.

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81970417) and the Fundamental Research Funds for the Central Universities (3332022117).