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Molecular Medicine Reports May 2024Recurrent miscarriage is used to refer to more than three pregnancy failures before 20 weeks of gestation. Defective trophoblast cell growth and invasion are frequently...
Recurrent miscarriage is used to refer to more than three pregnancy failures before 20 weeks of gestation. Defective trophoblast cell growth and invasion are frequently observed in recurrent miscarriage. Several microRNAs (miRs), including miR‑155‑5p, are aberrantly upregulated in recurrent miscarriage; however, the underlying molecular mechanisms remain unclear. The centrosome orchestrates microtubule networks and coordinates cell cycle progression. In addition, it is a base for primary cilia, which are antenna‑like organelles that coordinate signaling during development and growth. Thus, deficiencies in centrosomal functions can lead to several disease, such as breast cancer and microcephaly. In the present study, the signaling cascades were analyzed by western blotting, and the centrosome and primary cilia were observed and analyzed by immunofluorescence staining. The results showed that overexpression of miR‑155‑5p induced centrosome amplification and blocked primary cilia formation in trophoblast cells. Notably, centrosome amplification inhibited trophoblast cell growth by upregulating apoptotic cleaved‑caspase 3 and cleaved‑poly (ADP‑ribose) polymerase in miR‑155‑5p‑overexpressing trophoblast cells. In addition, overexpression of miR‑155‑5p inhibited primary cilia formation, thereby inhibiting epithelial‑mesenchymal transition and trophoblast cell invasion. All phenotypes could be rescued when cells were co‑transfected with the miR‑155‑5p inhibitor, thus supporting the role of miR‑155‑5p in centrosomal functions. It was also found that miR‑155‑5p activated autophagy, whereas disruption of autophagy via the depletion of autophagy‑related 16‑like 1 alleviated miR‑155‑5p‑induced apoptosis and restored trophoblast cell invasion. In conclusion, the present study indicated a novel role of miR‑55‑5p in mediating centrosomal function in recurrent miscarriage.
Topics: Pregnancy; Female; Humans; MicroRNAs; Trophoblasts; Cell Proliferation; Centrosome; Cell Movement; Abortion, Habitual
PubMed: 38551159
DOI: 10.3892/mmr.2024.13209 -
Cancer Metastasis Reviews Dec 2019Abdominal tumors (AT) in children account for approximately 17% of all pediatric solid tumor cases, and frequently exhibit embryonal histological features that... (Review)
Review
Abdominal tumors (AT) in children account for approximately 17% of all pediatric solid tumor cases, and frequently exhibit embryonal histological features that differentiate them from adult cancers. Current molecular approaches have greatly improved the understanding of the distinctive pathology of each tumor type and enabled the characterization of novel tumor biomarkers. As seen in abdominal adult tumors, microRNAs (miRNAs) have been increasingly implicated in either the initiation or progression of childhood cancer. Moreover, besides predicting patient prognosis, they represent valuable diagnostic tools that may also assist the surveillance of tumor behavior and treatment response, as well as the identification of the primary metastatic sites. Thus, the present study was undertaken to compile up-to-date information regarding the role of dysregulated miRNAs in the most common histological variants of AT, including neuroblastoma, nephroblastoma, hepatoblastoma, hepatocarcinoma, and adrenal tumors. Additionally, the clinical implications of dysregulated miRNAs as potential diagnostic tools or indicators of prognosis were evaluated.
Topics: Abdominal Neoplasms; Animals; Child; Humans; MicroRNAs
PubMed: 31848768
DOI: 10.1007/s10555-019-09829-x -
Microbial Pathogenesis Mar 2021Syphilis is a sexually transmitted disease of global prevalence. Current diagnostic methods lack sensitivity and specificity, which limits the early diagnosis and...
OBJECTIVES
Syphilis is a sexually transmitted disease of global prevalence. Current diagnostic methods lack sensitivity and specificity, which limits the early diagnosis and prognosis of the disease. MiRNAs hold great promise as potential biomarkers for infectious diseases diagnosis. We previously profiled the expression of miRNAs in PBMCs from patients with different stages of syphilis. We aimed to further confirm the miR-101-3p, miR-195-5p, and miR-223-3p expression profiles and evaluate their diagnostic value in syphilis infection.
METHODS
The expression levels of PBMC-derived miR-101-3p, miR-195-5p, and miR-223-3p were analyzed in 133 syphilis patients, 18 non-syphilis patients, and 23 healthy controls by RT-qPCR. ROC analysis was used to evaluate the differentiation power of these miRNAs in syphilis diagnosis, while the correlation between the expression of these miRNAs and TRUST titer was also statistically analyzed.
RESULTS
These miRNAs were significantly upregulated in syphilis patients in a stage-specific manner. ROC analysis indicated that miR-223-3p was powerful in discriminating between controls and patients with early, primary, secondary, and latent syphilis, as well as serological cure; the miR-195-5p/miR-223-3p panel showed an improved capacity to differentiate between syphilis patients, primary, or serofast-stage syphilis and controls, while the three miRNAs combined showed an improved capacity to differentiate latent syphilis or serological cure from controls. Importantly, miR-101-3p and miR-223-3p singly or jointly could specifically distinguish syphilis from non-syphilis patients. Moreover, TRUST titer was significantly correlated with miR-101-3p expression.
CONCLUSIONS
MiR-101-3p, miR-195-5p, and miR-223-3p might singly or jointly be potential diagnostic biomarkers at different stages of syphilis.
Topics: Biomarkers; Gene Expression Profiling; Humans; Leukocytes, Mononuclear; MicroRNAs; Syphilis
PubMed: 33524569
DOI: 10.1016/j.micpath.2021.104769 -
Essays in Biochemistry Sep 2022Cancer stem cells (CSCs) are a subgroup of tumor cells, possessing the abilities of self-renewal and generation of heterogeneous tumor cell lineages. They are believed... (Review)
Review
Cancer stem cells (CSCs) are a subgroup of tumor cells, possessing the abilities of self-renewal and generation of heterogeneous tumor cell lineages. They are believed to be responsible for tumor initiation, metastasis, as well as chemoresistance in human malignancies. MicroRNAs (miRNAs) are small noncoding RNAs that play essential roles in various cellular activities including CSC initiation and CSC-related properties. Mature miRNAs with ∼22 nucleotides in length are generated from primary miRNAs via its precursors by miRNA-processing machinery. Extensive studies have demonstrated that mature miRNAs modulate CSC initiation and stemness features by regulating multiple pathways and targeting stemness-related factors. Meanwhile, both miRNA precursors and miRNA-processing machinery can also affect CSC properties, unveiling a new insight into miRNA function. The present review summarizes the roles of mature miRNAs, miRNA precursors, and miRNA-processing machinery in regulating CSC properties with a specific focus on the related molecular mechanisms, and also outlines the potential application of miRNAs in cancer diagnosis, predicting prognosis, as well as clinical therapy.
Topics: Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Neoplasms; Neoplastic Stem Cells; Nucleotides
PubMed: 35996948
DOI: 10.1042/EBC20220007 -
Journal of Dental Research Dec 2023Several array-based microRNA (miRNA) expression studies independently showed increased expression of miRNAs hsa-miR-130a-3p, -142-3p, -144-3p, -144-5p, -223-3p, -17-5p,...
Several array-based microRNA (miRNA) expression studies independently showed increased expression of miRNAs hsa-miR-130a-3p, -142-3p, -144-3p, -144-5p, -223-3p, -17-5p, and -30e-5p in gingiva affected by periodontal inflammation. We aimed to determine direct target genes and signaling pathways regulated by these miRNAs to identify processes relevant to gingival inflammatory responses and tissue homeostasis. We transfected miRNA mimics (mirVana) for each of the 7 miRNAs separately into human primary gingival fibroblasts cultured from 3 different donors. Following RNA sequencing, differential gene expression and second-generation gene set enrichment analyses were performed. miRNA inhibition and upregulation was validated at the transcript and protein levels using quantitative reverse transcriptase polymerase chain reaction, Western blotting, and reporter gene assays. All 7 miRNAs significantly increased expression of the gene proto-oncogene, receptor tyrosine kinase (). Expression of known periodontitis risk genes , , and was significantly repressed by hsa-miR-130a-3p, -144-3p, and -144-5p, respectively. The genes , , , and showed the most significant and strongest downregulation after hsa-miR-142-3p, -17-5p, -223-3p, and -30e-5p transfection, respectively. The most significantly regulated gene set of each miRNA related to cell cycle (hsa-miRNA-144-3p and -5p [ = 4 × 10 and = 4 × 10], -miR-17-5p [ = 9.5 × 10], -miR-30e-5p [ = 8.2 × 10], -miR-130a-3p [ = 5 × 10]), integrin cell surface interaction (-miR-223-3p [ = 2.4 × 10]), and interferon signaling (-miR-142-3p [ = 5 × 10]). At the end of acute inflammation, gingival miRNAs bring together complex regulatory networks that lead to increased expression of the gene . This underscores the importance of mesenchymal cell migration and invasion during gingival tissue remodeling and proliferation in restoring periodontal tissue homeostasis after active inflammation. , a receptor of the mitogenic hepatocyte growth factor fibroblast secreted, is a core gene of this process.
Topics: Humans; Gingiva; MicroRNAs; Signal Transduction; Up-Regulation; Inflammation; Gene Expression Profiling
PubMed: 37822091
DOI: 10.1177/00220345231197984 -
PloS One 2020Approximately one-third of the patients with well-differentiated liposarcoma (WDLPS) will develop a local recurrence. Not much is known about the molecular relationship...
Approximately one-third of the patients with well-differentiated liposarcoma (WDLPS) will develop a local recurrence. Not much is known about the molecular relationship between the primary tumor and the recurrent tumor, which is important to reveal potential drivers of recurrence. Here we investigated the biology of recurrent WDLPS by comparing paired primary and recurrent WDLPS using microRNA profiling and genome-wide DNA methylation analyses. In total, 27 paired primary and recurrent WDLPS formalin-fixed and paraffin-embedded tumor samples were collected. MicroRNA expression profiles were determined using TaqMan® Low Density Array (TLDA) cards. Genome-wide DNA methylation and differentially methylated regions (DMRs) were assessed by methylated DNA sequencing (MeD-seq). A supervised cluster analysis based on differentially expressed microRNAs between paired primary and recurrent WDLPS did not reveal a clear cluster pattern separating the primary from the recurrent tumors. The clustering was also not based on tumor localization, time to recurrence, age or status of the resection margins. Changes in DNA methylation between primary and recurrent tumors were extremely variable, and no consistent DNA methylation changes were found. As a result, a supervised clustering analysis based on DMRs between primary and recurrent tumors did not show a distinct cluster pattern based on any of the features. Subgroup analysis for tumors localized in the extremity or the retroperitoneum also did not yield a clear distinction between primary and recurrent WDLPS samples. In conclusion, microRNA expression profiles and DNA methylation profiles do not distinguish between primary and recurrent WDLPS and no putative common drivers could be identified.
Topics: Adult; Aged; Cluster Analysis; DNA Methylation; Female; Gene Expression Regulation, Neoplastic; Genetic Heterogeneity; Humans; Liposarcoma; Male; MicroRNAs; Middle Aged; Neoplasm Recurrence, Local; Principal Component Analysis
PubMed: 31971976
DOI: 10.1371/journal.pone.0228014 -
Journal of Neuroinflammation Jan 2022Astrocytes are the most numerous glial cell type with important roles in maintaining homeostasis and responding to diseases in the brain. Astrocyte function is subject...
BACKGROUND
Astrocytes are the most numerous glial cell type with important roles in maintaining homeostasis and responding to diseases in the brain. Astrocyte function is subject to modulation by microRNAs (miRs), which are short nucleotide strands that regulate protein expression in a post-transcriptional manner. Understanding the miR expression profile of astrocytes in disease settings provides insight into the cellular stresses present in the microenvironment and may uncover pathways of therapeutic interest.
METHODS
Laser-capture microdissection was used to isolate human astrocytes surrounding stroke lesions and those from neurological control tissue. Astrocytic miR expression profiles were examined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Primary human fetal astrocytes were cultured under in vitro stress conditions and transfection of a miR mimic was used to better understand how altered levels of miR-210 affect astrocyte function. The astrocytic response to stress was studied using qPCR, enzyme-linked immunosorbent assays (ELISAs), measurement of released lactate, and Seahorse.
RESULTS
Here, we measured miR expression levels in astrocytes around human ischemic stroke lesions and observed differential expression of miR-210 in chronic stroke astrocytes compared to astrocytes from neurological control tissue. We also identified increased expression of miR-210 in mouse white matter tissue around middle cerebral artery occlusion (MCAO) brain lesions. We aimed to understand the role of miR-210 in primary human fetal astrocytes by developing an in vitro assay of hypoxic, metabolic, and inflammatory stresses. A combination of hypoxic and inflammatory stresses was observed to upregulate miR-210 expression. Transfection with miR-210-mimic (210M) increased glycolysis, enhanced lactate export, and promoted an anti-inflammatory transcriptional and translational signature in astrocytes. Additionally, 210M transfection resulted in decreased expression of complement 3 (C3) and semaphorin 5b (Sema5b).
CONCLUSIONS
We conclude that miR-210 expression in human astrocytes is modulated in response to ischemic stroke disease and under in vitro stress conditions, supporting a role for miR-210 in the astrocytic response to disease conditions. Further, the anti-inflammatory and pro-glycolytic impact of miR-210 on astrocytes makes it a potential candidate for further research as a neuroprotective agent.
Topics: Animals; Astrocytes; HeLa Cells; Humans; Inflammation; Laser Capture Microdissection; Mice; MicroRNAs; Stroke
PubMed: 34991629
DOI: 10.1186/s12974-021-02373-y -
CNS & Neurological Disorders Drug... 2015MicroRNAs (miRNAs) are ~22 nucleotide non-coding RNAs that control gene expression post-transcriptionally by base pairing to mRNAs. MiRNAs are predicted to target ~50%... (Review)
Review
MicroRNAs (miRNAs) are ~22 nucleotide non-coding RNAs that control gene expression post-transcriptionally by base pairing to mRNAs. MiRNAs are predicted to target ~50% of all protein-coding genes and functional studies indicate that they participate in the regulation of almost every cellular process. They also play a key role in pathogenetic mechanisms underlying several diseases, e.g. cancer, cardiovascular diseases, autoimmune diseases, and neurodegenerative diseases. Several miRNAs are expressed in the human brain where they contribute to equilibrium between maintenance and differentiation of neural stem cells. MiRNAs specific mechanisms of action and their roles in brain development and synaptic plasticity resulted in a great interest in the analysis of their potential role in the pathogenesis and pathophysiology of neuropsychiatric disorders. Currently, schizophrenia is one of the fields in psychiatry where miRNAs have been most widely investigated. The understanding of miRNAs role in schizophrenia has been achieved through association, functional and expression profiling studies on post mortem brain and peripheral tissues. Several studies identified association between neuropsychiatric disorders and variants in miRNAs including variations in miRNA/primary-/precursor-miRNAs sequences, in miRNAs biogenesis machinery genes, in the 3'UTR of target genes and in miRNAs expression. In summary, there is growing evidence that miRNAs exert a crucial role in gene expression regulation in the central nervous system and are altered in the development, presentation and response to treatment of psychiatric disorders. In this review we summarize the most significant results of experimental studies aimed at highlighting the involvement of human miRNAs in schizophrenia.
Topics: Animals; Humans; MicroRNAs; Schizophrenia
PubMed: 25613509
DOI: 10.2174/1871527314666150116124253 -
BMB Reports Jun 2016Innate immune responses are primary, relatively limited, and specific responses to numerous pathogens and toxic molecules. Protein expression involved in these innate... (Review)
Review
Innate immune responses are primary, relatively limited, and specific responses to numerous pathogens and toxic molecules. Protein expression involved in these innate responses must be tightly regulated at both transcriptional level and post-transcriptional level to avoid the development of excessive inflammation that can be potentially harmful to the host. MicroRNAs are small noncoding RNAs (~22 nucleotides [nts]) that participate in the regulation of numerous physiological responses by targeting specific messenger RNAs to suppress their translation. Recent work has shown that several negative regulators of transcription including microRNAs play important roles in inhibiting the exacerbation of inflammatory responses and in the maintenance of immunological homeostasis. This emerging research area will provide new insights on how microRNAs regulate innate immune signaling. It might show that dysregulation of microRNA synthesis is associated with the pathogenesis of inflammatory and infectious diseases. In this review, we focused on miR-146 and miR-125 and described the roles these miRNAs in modulating innate immune signaling. These microRNAs can control inflammatory responses and the outcomes of pathogenic infections. [BMB Reports 2016; 49(6): 311-318].
Topics: Animals; Gene Expression Regulation; Humans; Immunity, Innate; Inflammation; MicroRNAs; Signal Transduction; Toll-Like Receptors
PubMed: 26996343
DOI: 10.5483/bmbrep.2016.49.6.056 -
Frontiers in Bioscience (Scholar... Jun 2022Obesity and osteoporosis are global health problems characterized by high rates of prevalence and mortality due to complications. As people with visceral obesity age,... (Review)
Review
Obesity and osteoporosis are global health problems characterized by high rates of prevalence and mortality due to complications. As people with visceral obesity age, the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) increases, and adipocytes become the predominant stromal cells in the bone marrow microenvironment, which hinders the physiological regeneration and mineralization of bone tissue. Primary and secondary osteoporosis remain severe progressive diseases. Both osteoporosis and obesity are associated with microRNAs (miRNAs) that induce adipogenesis and osteoresorption. This review presents analyses of the roles and clinical potential of miRNAs in the epigenetic control of BMSC differentiation and the formation and function of osteoclasts in osteoporosis with and without obesity. Understanding the fine-tuned regulation of the expression of genes critical for the balance of osteogenesis/osteolysis processes may provide hope for the development of effective and safe osteoporosis therapies in the future.
Topics: Cell Differentiation; Humans; Mesenchymal Stem Cells; MicroRNAs; Obesity; Osteogenesis; Osteoporosis
PubMed: 36137980
DOI: 10.31083/j.fbs1403017