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Frontiers in Physiology 2020This review summarizes the current evidence for the involvement of proteotoxicity and protein quality control systems defects in diseases of the central nervous and...
This review summarizes the current evidence for the involvement of proteotoxicity and protein quality control systems defects in diseases of the central nervous and cardiovascular systems. Specifically, it presents the commonalities between the pathophysiology of protein misfolding diseases in the heart and the brain. The involvement of protein homeostasis dysfunction has been for long time investigated and accepted as one of the leading pathophysiological causes of neurodegenerative diseases. In cardiovascular diseases instead the mechanistic focus had been on the primary role of Ca dishomeostasis, myofilament dysfunction as well as extracellular fibrosis, whereas no attention was given to misfolding of proteins as a pathogenetic mechanism. Instead, in the recent years, several contributions have shown protein aggregates in failing hearts similar to the ones found in the brain and increasing evidence have highlighted the crucial importance that proteotoxicity exerts via pre-amyloidogenic species in cardiovascular diseases as well as the prominent role of the cellular response to misfolded protein accumulation. As a result, proteotoxicity, unfolding protein response (UPR), and ubiquitin-proteasome system (UPS) have recently been investigated as potential key pathogenic pathways and therapeutic targets for heart disease. Overall, the current knowledge summarized in this review describes how the misfolding process in the brain parallels in the heart. Understanding the folding and unfolding mechanisms involved early through studies in the heart will provide new knowledge for neurodegenerative proteinopathies and may prepare the stage for targeted and personalized interventions.
PubMed: 33584340
DOI: 10.3389/fphys.2020.625974 -
Cancer Medicine Oct 2019A series of studies have investigated the vital role of microRNA-181 (miR-181) in the initiation and development of colorectal cancer (CRC), and demonstrated that it... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A series of studies have investigated the vital role of microRNA-181 (miR-181) in the initiation and development of colorectal cancer (CRC), and demonstrated that it might be associated with the prognosis of CRC. However, inconsistent findings have hindered its clinical application.
METHODS
A comprehensive meta-analysis and an integrative bioinformatics analysis were carried out for concluding current available evidence, clarifying the preliminary prognostic value and unfolding the underlying biological function of miR-181 in CRC patients.
RESULTS
The findings revealed that elevated expression levels of miR-181 were associated with significantly poorer overall survival rates (HR = 1.75, 95% CI: 1.26-2.43, P < .05). Meanwhile, the target genes of miR-181 were identified and enriched into several important gene ontology (GO) categories and signaling pathways including miRNAs in cancer, pathways in cancer, proteoglycans in cancer, colorectal cancer, FoxO signaling pathway, PI3K-Akt signaling pathway, VEGF signaling pathway, HIF-1 signaling pathway, mTOR signaling pathway, and cAMP signaling pathway, which were confirmed highly involved in the initiation and progression of CRC. In addition, the protein-protein interaction (PPI) networks were set up by miR-181 targets to screen hub nodes and significant modules, which were also considerably associated with the molecular pathogenesis of CRC.
CONCLUSIONS
The present study demonstrated that miR-181 could be a promising biomarker with predictive value for prognosis for CRC patients. However, future studies comprising large cohorts from multicenter are warranted to further investigate the biomarker value of miR-181.
Topics: Biomarkers, Tumor; Colorectal Neoplasms; Humans; MicroRNAs; Prognosis; Survival Analysis
PubMed: 31448575
DOI: 10.1002/cam4.2520