CircNAP1L4 regulates pulmonary artery smooth muscle cell proliferation via the NAP1L4‐mediated super‐enhancer‐driven glycolysis gene hexokinase II (HK II) in pulmonary hypertension

• DOI: 10.1096/fj.202400585rrr
• Publication Date: 2024-08-05T16:53:15Z
• Authors: Xiaoying Wang; Xiaoyu Guan; Xiangrui Zhu; Lixin Zhang; Cui Ma; Siyu He; June Bai; Jian Mei; Qian Li; Na Sun; Bingxiang Wu; Daling Zhu
• Keywords: Male; 0301 basic medicine; Hypertension, Pulmonary; Myocytes, Smooth Muscle; RNA, Circular; Pulmonary Artery; Muscle, Smooth, Vascular; Mice; 03 medical and health sciences; Hexokinase; Humans; Animals; Glycolysis; Cells, Cultured; Research Article; Cell Proliferation

Abstract Glycolysis is a major determinant of pulmonary artery smooth muscle cell (PASMC) proliferation in hypertension (PH). Circular RNAs (circRNAs) are powerful regulators glycolysis multiple diseases; however, the role circRNAs PH has been poorly characterized. The aim this study was to uncover regulatory mechanism new circRNA, circNAP1L4, human (HPASMC) through host protein NAP1L4 regulate super‐enhancer‐driven gene hexokinase II (HK II). CircNAP1L4 downregulated hypoxic HPASMCs and plasma patients. Functionally, circNAP1L4 overexpression inhibited HPASMCs. Mechanistically, directly bound its affected ability move into nucleus epigenomic signals super‐enhancer HK II. Intriguingly, but not migration arterial endothelial cells (HPAECs) cocultured with Furthermore, pre‐mRNA‐processing‐splicing Factor 8 (PRP8) found production ratio linear NAP1L4. In vivo, targeting alleviates SU5416 combined hypoxia (SuHx)‐induced PH. Overall, these findings reveal circRNA that inhibits PASMC serves as therapeutic target for