CAMTA1 gene affects the ischemia-reperfusion injury by regulating CCND1

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.

Bioinformatics and Systems Biology Approach to Identify the Pathogenetic Link Between Psoriasis and Cardiovascular Disease

“… 62 Stroke is a leading cause of death associated with CVD, and ischemic stress can increase CCND1 levels in mature neurons, with the gene CAMTA1 known to regulate CCND1 expression levels and affect ischemic reperfusion injury during stroke. 63 STAT3 is involved in cell survival, differentiation, proliferation, angiogenesis, and immune activation, playing a vital role in the pathogenesis and development of psoriasis. 64 , 65 STAT3 activation is high in keratinocytes of human psoriasis lesions and aggravates psoriasis by promoting the proliferation, differentiation, and cytokine production of T cells.…”