Department of Experimental Biology, University of Jaen, 23071 Jaen, Spain.
Department of Human Anatomy and Embryology, Faculty of Medicine, Institute of Molecular Pathology Biomarkers, University of Extremadura, 06006 Badajoz, Spain.
Int J Mol Sci. 2023 Jun 8;24(12):9888. doi: 10.3390/ijms24129888.
The endoplasmic reticulum (ER) is a principal subcellular organelle responsible for protein quality control in the secretory pathway, preventing protein misfolding and aggregation. Failure of protein quality control in the ER triggers several molecular mechanisms such as ER-associated degradation (ERAD), the unfolded protein response (UPR) or reticulophagy, which are activated upon ER stress (ERS) to re-establish protein homeostasis by transcriptionally and translationally regulated complex signalling pathways. However, maintenance over time of ERS leads to apoptosis if such stress cannot be alleviated. The presence of abnormal protein aggregates results in loss of cardiomyocyte protein homeostasis, which in turn results in several cardiovascular diseases such as dilated cardiomyopathy (DCM) or myocardial infarction (MI). The influence of a non-coding genome in the maintenance of proper cardiomyocyte homeostasis has been widely proven. To date, the impact of microRNAs in molecular mechanisms orchestrating ER stress response has been widely described. However, the role of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) is just beginning to be addressed given the potential role of these RNA classes as therapeutic molecules. Here, we provide a current state-of-the-art review of the roles of distinct lncRNAs and circRNAs in the modulation of ERS and UPR and their impact in cardiovascular diseases.
内质网（ER）是负责分泌途径中蛋白质质量控制的主要亚细胞细胞器，防止蛋白质错误折叠和聚集。如果内质网（ER）不能缓解，内质网应激（ERS）触发的几种分子机制，如 ER 相关降解（ERAD）、未折叠蛋白反应（UPR）或内质网自噬，通过转录和翻译调节的复杂信号通路，重新建立蛋白质的体内平衡。然而，如果这种应激不能得到缓解，长时间维持 ERS 会导致细胞凋亡。异常蛋白质聚集体的存在导致心肌细胞蛋白质体内平衡的丧失，进而导致几种心血管疾病，如扩张型心肌病（DCM）或心肌梗死（MI）。非编码基因组在维持适当的心肌细胞体内平衡方面的作用已得到广泛证实。迄今为止，microRNAs 在协调 ER 应激反应的分子机制中的作用已被广泛描述。然而，长非编码 RNA（lncRNAs）和环状 RNA（circRNAs）的作用才刚刚开始被关注，因为这些 RNA 类具有作为治疗分子的潜在作用。在这里，我们提供了一个关于不同 lncRNAs 和 circRNAs 在调节 ER 应激和 UPR 及其在心血管疾病中的作用的最新综述。
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