The last two decades of cancer research have been devoted in two directions: (1) understanding the mechanism of carcinogenesis for an effective treatment, and (2) improving cancer prevention and screening for early detection of the disease. This last aspect has been developed, especially for certain types of cancers, thanks also to the introduction of new concepts such as liquid biopsies and precision medicine. In this context, there is a growing interest in the application of alternative and noninvasive methodologies to search for cancer biomarkers. The new frontiers of the research lead to a search for RNA molecules circulating in body fluids. Searching for biomarkers in extracellular body fluids represents a better option for patients because they are easier to access, less painful, and potentially more economical. Moreover, the possibility for these types of samples to be taken repeatedly, allows a better monitoring of the disease progression or treatment efficacy for a better intervention and dynamic treatment of the patient, which is the fundamental basis of personalized medicine. RNA molecules, freely circulating in body fluids or packed in microvesicles, have all the characteristics of the ideal biomarkers owing to their high stability under storage and handling conditions and being able to be sampled several times for monitoring. Moreover, as demonstrated for many cancers, their plasma/serum levels mirror those in the primary tumor. There are a large variety of RNA species noncoding for proteins that could be used as cancer biomarkers in liquid biopsies. Among them, the most studied are microRNAs, but recently the attention of the researcher has been also directed towards Piwi-interacting RNAs, circular RNAs, and other small noncoding RNAs. Another class of RNA species, the long noncoding RNAs, is larger than microRNAs and represents a very versatile and promising group of molecules which, apart from their use as biomarkers, have also a possible therapeutic role. In this review, we will give an overview of the most common noncoding RNA species detectable in extracellular fluids and will provide an update concerning the situation of the research on these molecules as cancer biomarkers.

https://www.mdpi.com/2072-6694/11/8/1170/pdf

Noncoding RNAs in Extracellular Fluids as Cancer Biomarkers: The New Frontier of Liquid Biopsies.

Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein.

MicroRNAs are small noncoding RNAs that modulate gene expression either directly, by impairing the stability and/or translation of transcripts that contain their specific target sequence, or indirectly through the targeting of transcripts that encode transcription factors, factors implicated in signal transduction pathways, or epigenetic regulators. Abnormal expression of micro-RNAs has been found in nearly all types of pathologies, including cancers. MiR-155 has been the first microRNA to be implicated in the regulation of the innate and adaptative immune responses, and its expression is either increased or decreased in a variety of liquid and solid malignancies. In this review, we examine the oncogenic and antitumor potentials of miR-155, with special emphasize on its dose-dependent effects. We describe the impact of miR-155 levels on antitumor activity of lymphocytes and myeloid cells. We discuss miR-155 dose-dependent effects in leukemias and analyze results showing that miR-155 intermediate levels tend to be detrimental, whereas high levels of miR-155 expression usually prove beneficial. We also examine the beneficial effects of high levels of miR-155 expression in solid tumors. We discuss the possible causal involvement of miR-155 in leukemias and dementia in individuals with Down's syndrome. We finally propose that increasing miR-155 levels in immune cells might increase the efficiency of newly developed cancer immunotherapies, due to miR-155 ability to target transcripts encoding immune checkpoints such as cytotoxic T lymphocyte antigen-4 or programmed death-ligand 1.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/gcc.22698

miR-155 expression in antitumor immunity: The higher the better?

Resveratrol (trans-3,5,4′-trihydroxystilbene, RSV) is a non-flavonoid dietary polyphenol with antioxidant, anti-inflammatory and anti-cancer properties that is primarily found in red berries. While RSV displays many beneficial effects in vitro, its actual effects in vivo or in animal models remain passionately debated. Recent publications suggest that RSV pleiotropic effects could arise from its capability to regulate the expression and activity of microRNAs, short regulators themselves capable of regulating up to several hundreds of target genes. In particular, RSV increases microRNA miR-663 expression in different human cell lines, suggesting that at least some of its multiple beneficial properties are through the modulation of expression of this microRNA. Indeed, the expression of microRNA miR-663 is reduced in certain cancers where miR-663 is considered to act as a tumor suppressor gene, as well as in other pathologies such as cardiovascular disorders. Target of miR-663 include genes involved in tumor initiation and/or progression as well as genes involved in pathologies associated with chronic inflammation. Here, we review the direct and indirect effects of RSV on the expression of miR-663 and its target transcripts, with emphasise on TGFβ1, and their expected health benefits, and argue that elucidating the molecular effects of different classes of natural compounds on the expression of microRNAs should help to identify new therapeutic targets and design new treatments.

https://www.mdpi.com/2305-6320/5/3/74/pdf

MiR-663, a MicroRNA Linked with Inflammation and Cancer That Is under the Influence of Resveratrol

The blood-brain barrier (BBB), which controls permeability into and out of the nervous system, is a tightly connected, structural, and functional separation between the central nervous system (CNS) and circulating blood. CNS diseases, such as Alzheimer's disease, multiple sclerosis, traumatic brain injury, stroke, meningitis, and brain cancers, often develop with the increased BBB permeability and further leads to irreversible CNS injury. Non-coding RNAs (ncRNAs) are functional RNA molecules that generally lack the coding abilities but can actively regulate the mRNA expression and function through different mechanisms. Various types of ncRNAs, including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), are highly expressed in brain microvascular endothelial cells and are potential mediators of BBB permeability. Here, we summarized the recent research progress on miRNA, lncRNA, and circRNA roles regulating the BBB permeability in different CNS diseases. Understanding how these ncRNAs affect the BBB permeability shall provide important therapeutic insights into the prevention and control of the BBB dysfunction.

https://www.tandfonline.com/doi/pdf/10.1080/15476286.2021.1950465

Non-coding RNAs: the extensive and interactive regulators of the blood-brain barrier permeability

MiR-155 deletion reduces ischemia-induced paralysis in an aortic aneurysm repair mouse model: Utility of immunohistochemistry and histopathology in understanding etiology of spinal cord paralysis.

Ian C. Davis

Papers

MiR-155 deletion reduces ischemia-induced paralysis in an aortic aneurysm repair mouse model: Utility of immunohistochemistry and histopathology in understanding etiology of spinal cord paralysis.