MicroRNAs (miRNAs) are small noncoding RNAs playing a fundamental role in the regulation of gene expression. Evidence accumulating in the past decades indicate that they are capable of simultaneously modulating diverse signaling pathways involved in a variety of pathophysiological processes. In the present review, we provide a comprehensive overview of the function of a highly conserved group of miRNAs, the miR-181 family, both in physiological as well as in pathological conditions. We summarize a large body of studies highlighting a role for this miRNA family in the regulation of key biological processes such as embryonic development, cell proliferation, apoptosis, autophagy, mitochondrial function, and immune response. Importantly, members of this family have been involved in many pathological processes underlying the most common neurodegenerative disorders as well as different solid tumors and hematological malignancies. The relevance of this miRNA family in the pathogenesis of these disorders and their possible influence on the severity of their manifestations will be discussed. A better understanding of the miR-181 family in pathological conditions may open new therapeutic avenues for devasting disorders such as neurodegenerative diseases and cancer.

https://www.mdpi.com/1422-0067/21/6/2092/pdf

The Pervasive Role of the miR-181 Family in Development, Neurodegeneration, and Cancer

The signaling pathway of the microtubule-associated protein kinase or extracellular regulated kinase (MAPK/ERK) is a common mechanism of extracellular information transduction from extracellular stimuli to the intracellular space The transduction of information leads to changes in the ongoing metabolic pathways and the modification of gene expression patterns In the central nervous system, ERK is expressed ubiquitously, both temporally and spatially As for the temporal ubiquity, this signaling system participates in three key moments: (i) Embryonic development; (ii) the early postnatal period; and iii) adulthood During embryonic development, the system is partly responsible for the patterning of segmentation in the encephalic vesicle through the FGF8-ERK pathway In addition, during this period, ERK directs neurogenesis migration and the final fate of neural progenitors During the early postnatal period, ERK participates in the maturation process of dendritic trees and synaptogenesis During adulthood, ERK participates in social and emotional behavior and memory processes, including long-term potentiation Alterations in mechanisms related to ERK are associated with different pathological outcomes Genetic alterations in any component of the ERK pathway result in pathologies associated with neural crest derivatives and mental dysfunctions associated with autism spectrum disorders The MAP-ERK pathway is a key element of the neuroinflammatory pathway triggered by glial cells during the development of neurodegenerative diseases, such as Parkinson's and Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis, as well as prionic diseases The process triggered by MAPK/ERK activation depends on the stage of development (mature or senescence), the type of cellular element in which the pathway is activated, and the anatomic neural structure However, extensive gaps exist with regards to the targets of the phosphorylated ERK in many of these processes

MAP/ERK Signaling in Developing Cognitive and Emotional Function and Its Effect on Pathological and Neurodegenerative Processes.

MicroRNAs: roles in cardiovascular development and disease

The study was used to probe long noncoding RNA X-inactive specific transcript (lncRNA XIST) RNA expression profile and its influence on cell cycle, proliferation, and apoptosis in myocardial cells. We also aimed to explore the possible meditating relationship between XIST, PDE4D, and miR-130a-3p. Gene differential analysis was carried out using human lncRNA Microarray V3.0. quantitative real-time PCR was used to test mRNA expressions of XIST, miR-130a-3p, and PDE4D in normal cells and postmyocardial infarction (MI) cells. Western blot was applied to determine the protein expression profile of PED4D. Changes in viability and cell cycle/apoptosis of post-MI myocardial cells after silencing of XIST or PDE4D were investigated by MTT assay and flow cytometry, respectively. The targeting relationship between miR-130a-3p and XIST, PDE4D in myocardial cells were verified by dual luciferase reporter assay. Simulated MI environment was constructed by performing anoxic preconditioning in normal cells to probe the influence of XIST on myocardial cell apoptosis. XIST and PDE4D were overexpressed in post-MI myocardial cells, whereas miR-130a-3p was underexpressed in post-MI myocardial cells. High-expressed XIST and PDE4D both promoted myocardial cell apoptosis. High-expressed XIST also inhibited myocardial cell proliferation. XIST-downregulated miR-130a-3p and PDE4D was a direct target of miR-130a-3p. LncRNA XIST promotes MI by targeting miR-130a-3p. MI induced by PDE4D can be reversed by miR-130a-3p.

LncRNA XIST regulates myocardial infarction by targeting miR-130a-3p.

A1/A2 astrocytes in central nervous system injuries and diseases: Angels or devils?

Negative Fgf8-Bmp2 feed-back is regulated by miR-130 during early cardiac specification

3-Nitropropionic acid (NPA) administration to rodents produces degeneration of the striatum, accompanied by neurological disturbances that mimic Huntington's disease (HD) motor neurological dysfunctions. It has been shown that inflammation mediates NPA-induced brain degeneration, and activated microglia secreting cytokines interleukin-1α (IL-1α) and tumor necrosis factor α (TNFα) can induce a specific type of reactive neurotoxic astrocytes, named A1, which have been detected in post-mortem brain samples of Huntington's, Alzheimer's, and Parkinson's diseases. In this work we used an experimental model based on the intraperitoneal (i.p.) administration of NPA to adult Wistar rats at doses that can elicit extensive brain degeneration, and brain samples were taken before and after extensive brain damage monitored using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Western blots and immunohistochemistry of brain slices show that i.p. NPA injections elicit significant increase in the expression levels of C3α subunit, a marker of generation of neurotoxic A1 astrocytes, and of cytokines IL-1α, TNFα, and C1q within the striatum, hippocampus, and cerebellum before the appearance of the HD-related neurological dysfunctions and neuronal death induced by NPA. Noteworthy, NPA administration primarily induces the generation of A1 astrocytes in the more recent phylogenetic area of the rat cerebellum. We conclude that the activation of complement C3 protein in the brain from Wistar rats is an early event in NPA-induced brain neurodegeneration.

https://www.mdpi.com/1422-0067/21/10/3609/pdf

Early Reactive A1 Astrocytes Induction by the Neurotoxin 3-Nitropropionic Acid in Rat Brain.

Reciprocal repression between Fgf8 and miR-133 regulates cardiac induction through Bmp2 signaling

Deep whole genome and transcriptome sequencing have highlighted the importance of an emerging class of non-coding RNA longer than 200 nucleotides (i.e., long non-coding RNAs (lncRNAs)) that are involved in multiple cellular processes such as cell differentiation, embryonic development, and tissue homeostasis. Cancer is a prime example derived from a loss of homeostasis, primarily caused by genetic alterations both in the genomic and epigenetic landscape, which results in deregulation of the gene networks. Deregulation of the expression of many lncRNAs in samples, tissues or patients has been pointed out as a molecular regulator in carcinogenesis, with them acting as oncogenes or tumor suppressor genes. Herein, we summarize the distinct molecular regulatory mechanisms described in literature in which lncRNAs modulate carcinogenesis, emphasizing epigenetic and genetic alterations in particular. Furthermore, we also reviewed the current strategies used to block lncRNA oncogenic functions and their usefulness as potential therapeutic targets in several carcinomas.

/pdf/molecular-mechanisms-of-lncrnas-in-the-dependent-regulation-2lezbpt1.pdf

Molecular Mechanisms of lncRNAs in the Dependent Regulation of Cancer and Their Potential Therapeutic Use

Kaempferol prevents the activation of complement C3 protein and the generation of reactive A1 astrocytes that mediate rat brain degeneration induced by 3-nitropropionic acid.

Virginio Garcia-Lopez

Papers

Negative Fgf8-Bmp2 feed-back is regulated by miR-130 during early cardiac specification

Early Reactive A1 Astrocytes Induction by the Neurotoxin 3-Nitropropionic Acid in Rat Brain.

Reciprocal repression between Fgf8 and miR-133 regulates cardiac induction through Bmp2 signaling

Molecular Mechanisms of lncRNAs in the Dependent Regulation of Cancer and Their Potential Therapeutic Use

Kaempferol prevents the activation of complement C3 protein and the generation of reactive A1 astrocytes that mediate rat brain degeneration induced by 3-nitropropionic acid.