CAMTA1 gene affects the ischemia-reperfusion injury by regulating CCND1

Yang Liu; Guohui Shang; Xuran Zhang; Fuyong Liu; Chi Zhang; Zhihao Li; Jing Jia; Yan Xu; Zhaojing Zhang; Shangdong Yang; Baixue Zhou; Yingying Luan; Yanyang Huang; Yue Peng; Tianyi Han; Ying He; Hong Zheng

doi:10.3389/fncel.2022.868291

CAMTA1 gene affects the ischemia-reperfusion injury by regulating CCND1

Front Cell Neurosci. 2022 Sep 9:16:868291. doi: 10.3389/fncel.2022.868291. eCollection 2022.

Authors

Yang Liu¹, Guohui Shang¹, Xuran Zhang², Fuyong Liu³, Chi Zhang¹, Zhihao Li¹, Jing Jia¹, Yan Xu¹, Zhaojing Zhang¹, Shangdong Yang¹, Baixue Zhou¹, Yingying Luan¹, Yanyang Huang¹, Yue Peng¹, Tianyi Han¹, Ying He¹, Hong Zheng¹

Affiliations

¹ Department of Medical Genetics and Cell Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
² Department of Clinical Laboratory, The First Affiliated Hospital of Henan University of CM, Henan University of CM, Zhengzhou, China.
³ Department of Pathogenic Biology and Immunology, School of Life Sciences, Sanquan College of Xinxiang Medical University, Xinxiang, China.

Abstract

Epigenetic modulations lead to changes in gene expression, including DNA methylation, histone modifications, and noncoding RNAs. In recent years, epigenetic modifications have been related to the pathogenesis of different types of cancer, cardiovascular disease, and other diseases. Emerging evidence indicates that DNA methylation could be associated with ischemic stroke (IS) and plays a role in pathological progression, but the underlying mechanism has not yet been fully understood. In this study, we used human methylation 850K BeadChip to analyze the differences in gene methylation status in the peripheral blood samples from two groups (3 IS patients vs. 3 healthy controls). According to their bioinformatics profiling, we found 278 genes with significantly different methylation levels. Seven genes with the most significant methylation modifications were validated in two expanded groups (100 IS patients vs. 100 healthy controls). The CAMTA1 gene had significantly different methylation changes in patients compared to the controls. To understand the CAMTA1 function in stroke, we generated CAMTA1 knockout in SH-SY5Y cells. RNA seq results in CAMTA1 knockout cells revealed the pathways and gene set enrichments involved in cellular proliferation and cell cycle. Furthermore, a series of experiments demonstrated that in the oxygen-glucose deprivation/re-oxygenation (OGD/R) model system, the expression of cyclin D1, an essential regulator of cell cycle progression, was increased in SH-SY5Y CAMTA1 KO cells. Increasing evidence demonstrated that ischemic stress could inappropriately raise cyclin D1 levels in mature neurons. However, the molecular signals leading to an increased cyclin D1 level are unclear. Our findings demonstrate for the first time that the CAMTA1 gene could regulate cyclin D1 expression and implicate their role in strokes.

Keywords: CAMTA1; CCND1; DNA methylation modification; cell cycle; ischemic stroke.