scholarly journals Emerging Clues of Regulatory Roles of Circular RNAs through Modulating Oxidative Stress: Focus on Neurological and Vascular Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Lingfei Li ◽  
Zhumei Ni ◽  
Xiaoli Si ◽  
Lin Jiang ◽  
Hongfei Sang ◽  
...  

Circular RNAs (circRNAs) are novel noncoding RNAs that play regulatory roles in gene expression. Dysregulation of circRNAs is associated with the development and progression of several diseases, such as diabetes mellitus, nervous system diseases, cardiovascular diseases, and cancer. CircRNAs functionally participate in cell physiological activities through various molecular mechanisms. However, these molecular mechanisms are unclear. Oxidative stress is an essential factor in the pathogenesis of various diseases, including neurological diseases. Emerging roles of circRNAs have been identified in different systems in response to oxidative stress. In this review, we summarize the current understanding of circRNA biogenesis, properties, expression profiles, and the clues indicating the regulatory roles of circRNAs through oxidative stress in various systems, especially the nervous system.

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Peng Li Zhou ◽  
Zhengyang Wu ◽  
Wenguang Zhang ◽  
Miao Xu ◽  
Jianzhuang Ren ◽  
...  

AbstractGrowing evidence has indicated that circular RNAs (circRNAs) play a pivotal role as functional RNAs in diverse cancers. However, most circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined, and the underlying molecular mechanisms mediated by circRNAs are largely unclear. Here, we screened human circRNA expression profiles in ESCC tissues and found significantly increased expression of hsa_circ_0000277 (termed circPDE3B) in ESCC tissues and cell lines compared to the normal controls. Moreover, higher circPDE3B expression in patients with ESCC was correlated with advanced tumor-node-metastasis (TNM) stage and dismal prognosis. Functional experiments demonstrated that circPDE3B promoted the tumorigenesis and metastasis of ESCC cells in vitro and in vivo. Mechanistically, bioinformatics analysis, a dual-luciferase reporter assay, and anti-AGO2 RNA immunoprecipitation showed that circPDE3B could act as a competing endogenous RNA (ceRNA) by harboring miR-4766-5p to eliminate the inhibitory effect on the target gene laminin α1 (LAMA1). In addition, LAMA1 was significantly upregulated in ESCC tissues and was positively associated with the aggressive oncogenic phenotype. More importantly, rescue experiments revealed that the oncogenic role of circPDE3B in ESCC is partly dependent on the miR-4766-5p/LAMA1 axis. Furthermore, bioinformatics analysis combined with validation experiments showed that epithelial-mesenchymal transition (EMT) activation was involved in the oncogenic functions of the circPDE3B–miR-4766-5p/LAMA1 axis in ESCC. Taken together, we demonstrate for the first time that the circPDE3B/miR-4766-5p/LAMA1 axis functions as an oncogenic factor in promoting ESCC cell proliferation, migration, and invasion by inducing EMT, implying its potential prognostic and therapeutic significance in ESCC.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6949 ◽  
Author(s):  
Jianning Chen ◽  
Qin Zou ◽  
Daojun Lv ◽  
Muhammad Ali Raza ◽  
Xue Wang ◽  
...  

Background Aging is a major risk factor for the development of many diseases, and the liver, as the most important metabolic organ, is significantly affected by aging. It has been shown that the liver weight tends to increase in rodents and decrease in humans with age. Pigs have a genomic structure, with physiological as well as biochemical features that are similar to those of humans, and have therefore been used as a valuable model for studying human diseases. The molecular mechanisms of the liver aging of large mammals on a comprehensive transcriptional level remain poorly understood. The pig is an ideal model animal to clearly and fully understand the molecular mechanism underlying human liver aging. Methods In this study, four healthy female Yana pigs (an indigenous Chinese breed) were investigated: two young sows (180-days-old) and two old sows (8-years-old). High throughput RNA sequencing was performed to evaluate the expression profiles of messenger RNA, long non-coding RNAs, micro RNAs, and circular RNAs during the porcine liver aging process. Gene Ontology (GO) analysis was performed to investigate the biological functions of age-related genes. Results A number of age-related genes were identified in the porcine liver. GO annotation showed that up-regulated genes were mainly related to immune response, while the down-regulated genes were mainly related to metabolism. Moreover, several lncRNAs and their target genes were also found to be differentially expressed during liver aging. In addition, the multi-group cooperative control relationships and constructed circRNA-miRNA co-expression networks were assessed during liver aging. Conclusions Numerous age-related genes were identified and circRNA-miRNA co-expression networks that are active during porcine liver aging were constructed. These findings contribute to the understanding of the transcriptional foundations of liver aging and also provide further references that clarify human liver aging at the molecular level.


2021 ◽  
Vol 84 ◽  
pp. 1-11
Author(s):  
Artem Huslystyi ◽  
Victor Nedzvetsky ◽  
Serhii Yermolenko ◽  
Viktor Gasso ◽  
Vladyslav Petrushevskyi ◽  
...  

Imidacloprid is a widely used pesticide that belongs to the class of neonicotinoids. There is a piece of rising evidence that neonicotinoids exert cytotoxic effects in non-target organisms including vertebrate species such as mammals. Nevertheless, dose-limiting toxicity and molecular mechanisms of neonicotinoids' deleterious effects are still poorly understood. In accord to imidacloprid fate in the environment, the most of used pesticide is absorbed in the soil. Therefore, earthworms, which are prevailing soil organisms, could be considered as a target of neonicotinoids toxicity. The earthworm’s simple nervous system is a prospective model for neurotoxicological studies. We exposed earthworms to imidacloprid in a paper contact test with a doses range of 0.1‑0.4 µg/cm2 for 14 days. In the present work, we studied the imidacloprid effect on oxidative stress generation and neuronal marker neuron-specific enolase (NSE) expression. The exposure to imidacloprid induced a dose-dependent decrease in NSE. Both reactive oxygen species production and lipid peroxidation level were upregulated as well. Observed NSE decline suggests imidacloprid-caused disturbance in earthworm neuron cells. Obtained data have shown that relatively low doses of imidacloprid are potent to induce cytotoxicity in neurons. Furthermore, neurotoxicity could be recognized as one of an individual scenario of the general imidacloprid toxicity. Thus, presented results suggest the cytotoxicity of imidacloprid low doses in non-target organisms and hypothesize that NSE downregulation could be estimated as a biomarker of neonicotinoid cytotoxicity in a nervous system of non-insect species.


2021 ◽  
Author(s):  
Bita Hassani ◽  
Hasan Mollanoori ◽  
Farkhondeh Pouresmaeili ◽  
Yazdan Asgari ◽  
Soudeh Ghafouri-Fard

Abstract Background. Luminal tumors are the utmost frequent subtype of breast cancer (BC). Despite luminal BC has relatively good prognosis, in a subset of patients, disease relapse occursto endocrine therapy ;hence, there is a critical need to identify new strategies to promote the early detection and more effective therapies. Noncoding RNAs including microRNAs, long noncoding RNAs, and circular RNAs can interact with and modulate each other via diverse molecular mechanisms and make a complicated regulatory network.ncRNAs participate in diverse biological processes and disorders such as breast tumors. Therefore, understanding their regulatory mechanisms allow to develop new field of research and therapeutic options for BC patients.Methods. In this study, BC-specific RNA expression profiles including mRNAs, miRNAs, lncRNAs, and circRNAs were retrievedfrom Gene Expression Omnibus microarray datasets, and differentially expressed(DE) items were obtained. Disease ontology, functional and pathway enrichment analyses were executed. The protein-protein interaction network was constructed, and hub mRNAs were extracted.The prognostic value of hub mRNAs in patients of BC were performed. Subsequently, a ceRNA network was established.Results. In total, 691 DE genes, 122 DE lncRNAs, 60 DE miRNAs, and 38 DE circRNAs in breast tumor samples were compared with normal samples. Subsequently, 12 hub-genesincluding FOXO3, RHOA, EZH2, KIT, HSP90B1, NCOA3, RAC1, IGF1, CAV1, CXCR4, CCNB1, and ITGB1 were screened from the network. Kaplan-Meier Plotter results revealed that FOXO3 and RHOA were a suitable prognostic marker for patients with breast cancer. Finally, we determined possible ncRNAs (circ0007535, circ0002727, circ0005240, circ0014130, circ0044927, circ0007001, circ0089153,NORAD, MALAT1, TUG1, ZFAS1, OPI5-AS1, miR183,miR182, miR101, miR200c, miR200b, miR149, miR342, and miR1207) which could crosstalk with each other to regulateFOXO3 and RHOA through different regulatory patterns. Conclusion. These data might improve our perception of the breast tumorigenesis and could develop new field of research and therapeutic options for BC patients.


2020 ◽  
Vol 8 (38) ◽  
pp. 8748-8767
Author(s):  
Zhen An ◽  
Jincong Yan ◽  
Ye Zhang ◽  
Renjun Pei

Nanomaterials with excellent ROS-scavenging ability and biodistribution are considered as promising candidates in alleviating oxidative stress and restoring redox balance in CNS diseases, further facilitating the function recovery of the CNS.


2021 ◽  
Author(s):  
Peihong Wang ◽  
Sai Wang ◽  
Yan Wu ◽  
Wenhan Nie ◽  
Ayizekeranmu Yiming ◽  
...  

Abstract BackgroundThe emerging role of circular RNAs (circRNAs) in various biological processes have advanced our knowledge of transcriptional and post-transcriptional gene regulation. The number and expression of plant circRNAs vary with species and treatments. However, the expression profile and the potential role of circRNAs during plant response to pathogen invasion are still elusive. ResultsIn this study, we identified 3517 circRNAs from PXO99A-infected rice leaves using the ribosomal RNA (rRNA) depleted RNA-Sequencing technique coupled with the CIRI2 and CIRCexplorer2 pipeline. Among them, 2994 (85.13%) circRNAs arised from the exons of their parent genes, 1214 circRNAs were previously unknown and 276 circRNAs exhibited differential expression profiles upon PXO99A infection over time. In addition, 31 differentially expressed circRNAs (DEcircRNAs) were predicted as the corresponding 121 miRNAs sponges. Functional analysis of both host genes and target mRNAs suggested that these identified circRNAs might play an important role in reprogramming rice responses to PXO99A invasion, mainly by mediating photorespiration, chloroplast, peroxisome and diterpenoid biosynthesis associated pathways.ConclusionThese results inferred a potential functional role of circRNAs in the regulation of rice immunity and provide novel clues for revealing the molecular mechanisms of rice-PXO99A interaction.


2020 ◽  
Vol 35 (4) ◽  
pp. 224-235
Author(s):  
Fuzhou Wang

Optogenetics is an emerging branch of biology that combines genetics and optics to achieve precise light control of specific cells in organisms. It is a method of studying excitable cells that uses proteins that are embedded in the cell membrane and are activated by light (i.e. “opto”). Such proteins (opsins) are found in most animals in the retina of the eyes, as well as in some plants, such as green algae. In order to integrate photoactivated proteins into neuronal membranes, it is necessary to introduce rhodopsin genes obtained from other organisms into neurons, hence the “genetics”. Optogenetics is widely used in the field of modern neurobiology, and plays an essential role in the study of the mechanism of neural circuits, behaviors, central nervous system diseases, and mental disorders. Based on the development of optogenetics technology, this paper introduces its optimization and localization expression, which not only provides references for the research and development of optogenetics, but also provides the possibility for in-depth research and treatment of neurological diseases.


2021 ◽  
Vol 22 (14) ◽  
pp. 7432
Author(s):  
Tapan Behl ◽  
Rashita Makkar ◽  
Aayush Sehgal ◽  
Sukhbir Singh ◽  
Neelam Sharma ◽  
...  

The human body is highly complex and comprises a variety of living cells and extracellular material, which forms tissues, organs, and organ systems. Human cells tend to turn over readily to maintain homeostasis in tissues. However, postmitotic nerve cells exceptionally have an ability to regenerate and be sustained for the entire life of an individual, to safeguard the physiological functioning of the central nervous system. For efficient functioning of the CNS, neuronal death is essential, but extreme loss of neurons diminishes the functioning of the nervous system and leads to the onset of neurodegenerative diseases. Neurodegenerative diseases range from acute to chronic severe life-altering conditions like Parkinson’s disease and Alzheimer’s disease. Millions of individuals worldwide are suffering from neurodegenerative disorders with little or negligible treatment available, thereby leading to a decline in their quality of life. Neuropathological studies have identified a series of factors that explain the etiology of neuronal degradation and its progression in neurodegenerative disease. The onset of neurological diseases depends on a combination of factors that causes a disruption of neurons, such as environmental, biological, physiological, and genetic factors. The current review highlights some of the major pathological factors responsible for neuronal degradation, such as oxidative stress, cell death, and neuroinflammation. All these factors have been described in detail to enhance the understanding of their mechanisms and target them for disease management.


2015 ◽  
Vol 93 (12) ◽  
pp. 1021-1027 ◽  
Author(s):  
Luc Rochette ◽  
Steliana Ghibu ◽  
Adriana Muresan ◽  
Catherine Vergely

Diabetes is a chronic metabolic disease with a high prevalence worldwide. Diabetes and insulin resistance are associated with the development of cardiovascular and nervous diseases. The development of these disorders reflects complex pathological processes in which the oxidative stress caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) plays a pivotal role. It is widely accepted that diabetes impairs endothelial nitric oxide synthase (eNOS) activity and increases the production of ROS, thus resulting in diminished NO bioavailability and increased oxidative stress. Alpha-lipoic acid (LA) possesses beneficial effects both in the prevention and in the treatment of diabetes. LA is a potent antioxidant with insulin-mimetic and anti-inflammatory activity. LA in the diet is quickly absorbed, transported to the intracellular compartments, and reduced to dihydrolipoic acid (DHLA) under the action of enzymes. LA, which plays an essential role in mitochondrial bioenergetic reactions, has drawn considerable attention as an antioxidant for use in managing diabetic complications such as retinopathy, neuropathy and other vascular diseases.


2013 ◽  
Vol 71 (10) ◽  
pp. 815-817 ◽  
Author(s):  
Marleide da Mota Gomes ◽  
Eliasz Engelhardt

Jean-Martin Charcot was a pioneer in a variety of subjects, including nervous system diseases; anatomy; physiology; pathology; and diseases of ageing, joints, and lungs. His medical achievements were mainly based on his anatomopathological proficiency, his observation, and his personal thoroughness that favored the delineation of the nosology of the main neurological diseases, including multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease, peroneal muscular atrophy, and hysteria/epilepsy. The link of this anatomoclinical method with iconographic representations and theatrical lessons, and the rich bibliographical documentations, carried out in a crowded diseased people barn - Salpetrière hospital were the basis of his achievements, which are still discussed 120 years after his death.


Sign in / Sign up

Export Citation Format

Share Document