RESUMO
Cardiovascular diseases (CVDs) are multifactorial chronic diseases and have the highest rates of morbidity and mortality worldwide. The ubiquitin-proteasome system (UPS) plays a crucial role in posttranslational modification and quality control of proteins, maintaining intracellular homeostasis via degradation of misfolded, short-lived, or nonfunctional regulatory proteins. Noncoding RNAs (ncRNAs, such as microRNAs, long noncoding RNAs, circular RNAs and small interfering RNAs) serve as epigenetic factors and directly or indirectly participate in various physiological and pathological processes. NcRNAs that regulate ubiquitination or are regulated by the UPS are involved in the execution of target protein stability. The cross-linked relationship between the UPS, ncRNAs and CVDs has drawn researchers' attention. Herein, we provide an update on recent developments and perspectives on how the crosstalk of the UPS and ncRNAs affects the pathological mechanisms of CVDs, particularly myocardial ischemia/reperfusion injury, myocardial infarction, cardiomyopathy, heart failure, atherosclerosis, hypertension, and ischemic stroke. In addition, we further envision that RNA interference or ncRNA mimics or inhibitors targeting the UPS can potentially be used as therapeutic tools and strategies.
Assuntos
Doenças Cardiovasculares , MicroRNAs , Humanos , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Ubiquitina , Ligases , RNA não Traduzido/genética , MicroRNAs/genética , Complexo de Endopeptidases do ProteassomaRESUMO
Ferroptosis is a novel form of programmed cell death, and it is characterized by iron-dependent oxidative damage, lipid peroxidation and reactive oxygen species accumulation. Notable studies have revealed that ferroptosis plays vital roles in tumor occurrence and that abundant ferroptosis in cells can inhibit tumor progression. Recently, some noncoding RNAs (ncRNAs), particularly microRNAs, long noncoding RNAs, and circular RNAs, have been shown to be involved in biological processes of ferroptosis, thus affecting cancer growth. However, the definite regulatory mechanism of this phenomenon is still unclear. To clarify this issue, increasing studies have focused on the regulatory roles of ncRNAs in the initiation and development of ferroptosis and the role of ferroptosis in progression of various cancers, such as lung, liver, and breast cancers. In this review, we systematically summarized the relationship between ferroptosis-associated ncRNAs and cancer progression. Moreover, additional evidence is needed to identify the role of ferroptosis-related ncRNAs in cancer progression. This review will help us to understand the roles of ncRNAs in ferroptosis and cancer progression and may provide new ideas for exploring novel diagnostic and therapeutic biomarkers for cancer in the future.
Assuntos
Neoplasias da Mama , Ferroptose , RNA Longo não Codificante , Feminino , Ferroptose/genética , Humanos , RNA Circular/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismoRESUMO
The high-mortality rate of cardiovascular diseases (CVDs) is associated with the myocardial ischemia and reperfusion (I/R). Recent investigations have revealed that microRNAs (miRNAs) exert vital functions in the apoptosis of cardiomyocyte cell. Nevertheless, the potential role of miR-30a-5p in the regulation of cardiomyocyte cell apoptosis needs to be illuminated. In the current study, we observed that hypoxia/reoxygenation (H/R) remarkably raised the level of miR-30a-5p but reduced the expression of E2F transcription factor 3 (E2F3) in H9c2 cardiomyocytes. In vivo, miR-30a-5p was found to be significantly upregulated in the hearts of rats following I/R. Downregulation of miR-30a-5p using anti-miR-30a-5p decreased H9c2 cardiomyocytes apoptosis caused by H/R and promoted the proliferation of H9c2 inhibited by H/R. Moreover, E2F3 was a possible target gene of miR-30a-5p and upregulation of miR-30a-5p reduced the expression level of E2F3 in H9c2 cardiomyocytes. We further identified that E2F3 silencing reversed the effect of anti-miR-30a-5p on the proliferation and apoptosis in H/R treated H9c2 cells. These studies suggested that downregulation of miR-30a-5p attenuated the impact of H/R on H9c2 cardiomyocytes through targeting E2F3.
