Browsing by Subject "MicroRNAs"

Now showing 1 - 7 of 7
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    Intratumor heterogeneity in human parathyroid tumors
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Verdelli, C.; Tavanti, G.S.; Corbetta, S.
    Parathyroid tumors are the second most common endocrine neoplasia after thyroid neoplasia. They are mostly associated with impaired parathormone (PTH) synthesis and release determining the metabolic and clinical condition of primary hyperparathyroidism (PHPT). PHPT is the third most prevalent endocrine disorder, mainly affecting postmenopausal women. Parathyroid benign tumors, both adenomas of a single gland or hyperplasia involving all the glands, are the main histotypes, occurring in more than 95% of PHPT cases. The differential diagnosis between benign and malignant parathyroid lesions is a challenge for clinicians. It relies on histologic features, which display significant overlap between the histotypes with different clinical outcomes. Parathyroid adenomas and hyperplasia have been considered so far as a unique monoclonal/polyclonal entity, while accumulating evidence suggest great heterogeneity. Intratumor parathyroid heterogeneity involves tumor cell type, as well as tumor cell function, in terms of PTH synthesis and secretion, and of expression patterns of membrane and nuclear receptors (calcium sensing receptor, vitamin D receptor, α-klotho receptor and others). Intratumor heterogeneity can also interfere with cell molecular biology, in regard to clonality, oncosuppressor gene expression (such as MEN1 and HRPT2/CDC73), transcription factors (GCM2, TBX1) and microRNA expression. Such heterogeneity is likely involved in the phenotypic variability of the parathyroid tumors, and it should be considered in the clinical management, though at present target therapies are not available, with the exception of the calcium sensing receptor agonists.
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    Mesenchymal stem cell-derived microRNAs: friends or foes of tumor cells?
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Harrell, Carl Randall; Djonov, Valentin; Volarevic, Vladislav
    Mesenchymal stem cell (MSC)-dependent biological effects in the tumor microenvironment mainly rely on the activity of MSC-sourced microRNAs (MSCmiRNAs) which modulate protein synthesis in target tumor cells, endothelial cells and tumor-infiltrated immune cells, regulating their phenotype and function. Several MSC-sourced miRNAs (miR-221, miR-23b, miR-21-5p, miR-222/223, miR-15a miR-424, miR-30b, miR-30c) possess tumor-promoting properties and are able to enhance viability, invasiveness and metastatic potential of malignant cells, induce proliferation and sprouting of tumor endothelial cells and suppress effector functions of cytotoxic tumor-infiltrated immune cells, crucially contributing to the rapid growth and progression of tumor tissue. On the contrary, MSCs also produce “anti-tumorigenic” miRNAs (miR-100, miR222-3p, miR-146b miR-302a, miR-338-5p, miR-100-5p and miR-1246) which suppress tumor growth and progression by: up-regulating expression of chemoresistance-related genes in tumor cells, by suppressing neo-angiogenesis and by inducing generation of tumorotoxic phenotypes in tumor-infiltrated lymphocytes. In this review article, we summarize the current knowledge about molecular mechanisms that are responsible for MSC-miRNA-dependent alterations of intracellular signaling in tumor and immune cells and we discuss different insights regarding the therapeutic potential of MSC-derived miRNAs in cancer treatment.
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    MicroRNAs regulate APOBEC gene expression
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Cao, Wei; Wu, Wei
    Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) is a family of evolutionarily conserved cytidine deaminases, encoded by eleven genes located in the human genome. APOBECs play key roles in innate immunity through their ability to mutagenize viral DNA and restrict viral replication. Recent cancer genomics revealed APOBEC3 subtype-mediated APOBEC-signature mutations are common in a broad spectrum of human cancers. The pervasive APOBEC3 activation in the host genome which converts cytosine to uracile during RNA editing has been suggested to depend on ATR/chk1 pathways. In this review, we highlight how microRNAs interact with the APOBEC gene family and post-transcriptionally regulate APOBEC gene expression, and we speculate how targeting specific microRNAs may reduce host genome mutagenesis via inactivation of APOBEC deaminases.
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    MicroRNAs: a critical regulator under mechanical force
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Wei, Fulan; Yang, Shuangyan; Wang, Songlin
    Mechanical force is a kind of mechanical stimuli which actively participates in manipulating cellular activities in numerous types of cells. Progress in molecular and genetic research has uncovered various regulatory mechanisms underlying mechanical forceinduced changes in cellular activities, which include both transcriptional regulation and post-transcriptional regulation. MicroRNAs (miRNAs) are 20-25 nucleotide (nt) non-coding RNAs which serve as posttranscriptional regulators of multiple physiological processes. To date, considerable research effort has focused on the expressions and functions of miRNAs in a wide range of biological and pathological processes, including but not limited to development, proliferation, metabolism and osteogenic differentiation. In this review, major emphasis is placed on the biogenesis, expressions and functions of miRNAs in a mechanical environment.
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    MiR-124-3p attenuates brain microvascular endothelial cell injury in vitro by promoting autophagy
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Zhao, Jing; Wang, Yan; Wang, Dong; Yan, Wei; Zhang, Shishuang; Li, Dai; Han, Zhaoli; Chen, Fanglian; Le, Ping
    . Traumatic brain injury (TBI) can cause the pathological disruption of the blood-brain barrier (BBB) and associated neurological injury. Reducing the severity of such barrier disruption following TBI can decrease the degree of brain edema, suppress intracranial inflammation, and thereby protect against neurological damage. The BBB is made up of brain microvascular endothelial cells (BMVECs), neurons, pericytes, astrocytes, and extracellular matrix components. In prior analyses, we have demonstrated that miR-124-3p expression is enhanced in microglia-derived exosomes following TBI, with this miRNA being capable of promoting neural repair after such injury. Based upon these results, the present study was formulated to examine the impact of miR-124-3p on BMVEC function and to evaluatethe mechanistic basis for its activity by overexpressing miR-124-3p in these endothelial cells. We utilized a bEnd.3 cell scratch wound in vitro model to simulate TBI-associated brain microvascular endothelial cell injury. Lipofectamine3000 was used to transfect endothelial cells such that they overexpressed miR-124-3p. Fluorescence microscopy was used to observe the effects of miR-124-3p expression on these endothelial cells. TUNEL+CD31 immunofluorescence stainingwas employed to observe endothelial cell apoptosis. Tight junctions were observed via ionconductivity microscopy. Western blotting was used to detect the expression of tight junction proteins (occludin, ZO-1), autophagy-associated proteins (Beclin1, p62, LC3-II/LC3-I), and mTOR-associated proteins (p-mTOR, PDE4B). Chloroquine was used to treat these injured endothelial cells overexpressing miR-124-3p, and endothelial cell apoptosis was assessed via TUNEL+CD31 immunofluorescence staining. We found that the upregulation of miR-124-3p was sufficient to suppress bEnd.3 cell apoptotic death following in vitro scratch injury while promoting the upregulation of the tight junction proteins ZO-1 and occludin in these cells, thereby reducing the degree of leakage across the cerebral microvascular endothelial barrier. These protective effects may be related to the ability of miR124-3p to suppress mTOR signaling and to induce autophagic activity within BMVECs. These data support a model wherein miR-124-3p can inhibit mTOR signaling and promote autophagic induction in BMVECs, thereby protecting these cells against TBIinduced damage.
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    MiRNAs participate in the diagnosis, pathogenesis and therapy of Parkinson's disease
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Lu, Xuexin; Cui, Zhijie; Liu, Shuang; Yin, Feng
    MicroRNAs (miRNAs), one kind of posttranscriptional modification, mediate transcriptional silencing of various metabolic enzymes that are involved in various life processes, including Parkinson’s disease. At present, the pathogenesis of Parkinson's disease is not clear, although many studies suggest that miRNAs play a very important role in the progress of Parkinsonism. This paper reviews the biological characteristics of miRNAs and summarizes the progress of miRNAs in reference to the diagnosis and pathogenesis of Parkinson’s disease. It even considers miRNAs as a potential target for Parkinson’s disease therapy
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    Regulatory role of microRNAs in the proliferation and differentiation of adipose-derived stem cells
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Yeong Kim, Doo; Sung, Jong Hyuk
    Adipose-derived stem cells (ASCs) are multipotent mesenchymal stem cells obtained from stromal-vascular fraction of adipose tissue. ASCs are a promising resource for cell therapy due to their simple isolation, extensive expansion potential, and low immunogenicity. ASCs repair and regenerate damaged tissue by direct differentiation, whereas many other approaches rely on the secretion of paracrine factors. miRNAs target mRNAs for cleavage or translational repression, and have been shown to play critical roles in the regulation of stem cell proliferation and differentiation. The miRNA expression profile of ASCs varies according to the isolation and culturing method, and more than 40 different miRNAs have been reported to regulate ASC proliferation and differentiation. Therefore, this review summarizes the ASC-related miRNAs and their pivotal roles in regulating the proliferation and differentiation of ASCs. A comprehensive understanding of the effects of miRNAs on the proliferation and differentiation of ASCs is important and useful to enhance the regenerative potential of ASCs.