scholarly journals Ulipristal Acetate Modifies miRNA Expression in Both Superficial and Basal Layers of the Human Endometrium

2021 ◽  
Vol 10 (19) ◽  
pp. 4442
Author(s):  
Kamila Kolanska ◽  
Maria Sbeih ◽  
Geoffroy Canlorbe ◽  
Arsène Mekinian ◽  
Justine Varinot ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Basal Layer ◽  
Superficial Layer ◽  
Human Endometrium ◽  
Tissue Samples ◽  
Ulipristal Acetate ◽  
Receptor Modulator

(1) Background: Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM) widely used for emergency contraception and mid- to long-term leiomyoma treatment. The aim of this study was to identify modifications of miRNA expression in superficial and basal layers of the human endometrium at the end of the UPA treatment for at least 3 months. (2) Methods: Microarray miRNA analysis of formalin-fixed, paraffin-embedded hysterectomy tissue samples was conducted, followed by an Ingenuity Pathway Analysis. Samples were divided into three groups: women having had 3 months of UPA treatment (n = 7); and two control groups of UPA-naïve women in the proliferative (n = 8) or secretory (n = 6) phase. (3) Results: The UPA modified the expression of 59 miRNAs involved in the processes of cell cycle, carcinogenesis, and inflammation. Their expression profiles were different in the basal and superficial layers. Most of the processes influenced by the UPA in the basal layer were connected to the cell cycle and immune regulation. (4) Conclusion: Specific changes were observed in both layers of the endometrium in the UPA group. However, the miRNA expression in the basal layer was not consistent with that in the superficial layer. Other large studies analysing the long-term impact of SPRM on endometrial miRNA expression are necessary.

scholarly journals Overexpression of β-Arrestins inhibits proliferation and motility in triple negative breast cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saber Yari Bostanabad ◽  
Senem Noyan ◽  
Bala Gur Dedeoglu ◽  
Hakan Gurdal
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cell Function ◽  
Expression Profiles ◽  
Tissue Samples ◽  
Expression Levels ◽  
Cell Cycle Genes

Abstractβ-Arrestins (βArrs) are intracellular signal regulating proteins. Their expression level varies in some cancers and they have a significant impact on cancer cell function. In general, the significance of βArrs in cancer research comes from studies examining GPCR signalling. Given the diversity of different GPCR signals in cancer cell regulation, contradictory results are inevitable regarding the role of βArrs. Our approach examines the direct influence of βArrs on cellular function and gene expression profiles by changing their expression levels in breast cancer cells, MDA-MB-231 and MDA-MB-468. Reducing expression of βArr1 or βArr2 tended to increase cell proliferation and invasion whereas increasing their expression levels inhibited them. The overexpression of βArrs caused cell cycle S-phase arrest and differential expression of cell cycle genes, CDC45, BUB1, CCNB1, CCNB2, CDKN2C and reduced HER3, IGF-1R, and Snail. Regarding to the clinical relevance of our results, low expression levels of βArr1 were inversely correlated with CDC45, BUB1, CCNB1, and CCNB2 genes compared to normal tissue samples while positively correlated with poorer prognosis in breast tumours. These results indicate that βArr1 and βArr2 are significantly involved in cell cycle and anticancer signalling pathways through their influence on cell cycle genes and HER3, IGF-1R, and Snail in TNBC cells.

scholarly journals Baicalein, a Natural Anti-Cancer Compound, Alters MicroRNA Expression Profiles in Bel-7402 Human Hepatocellular Carcinoma Cells

2017 ◽  
Vol 41 (4) ◽  
pp. 1519-1531 ◽  
Author(s):  
Beibei Bie ◽  
Jin Sun ◽  
Jun Li ◽  
Ying Guo ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Akt Pathway ◽  
Qrt Pcr ◽  
Cycle Arrest ◽  
Mirna Expression Profiles

Background/Aims: Baicalein has been shown to possess significant anti-hepatoma activity by inhibiting cell proliferation. Whether the anti-proliferative effect of baicalein is related to its modulation of miRNA expression in hepatocellular carcinoma (HCC) is still unknown. Methods: The anti-proliferative effects of baicalein on HCC cell line Bel-7402 was assessed by detecting the proliferation activity, cell cycle distribution, expression changes of p21/CDKN1A, P27/CDKN1B, total Akt and phosphoryted AKT. Microarray analysis was conducted to determine the miRNA expression profiles in baicalein-treated or untreated Bel-7402 cells and then validated by qRT-PCR in two HCC cell lines (Bel-7402 and Hep3B). The gain-of-function of miR-3127-5p was performed by detecting anti-proliferative effects after transfecting miRNA mimics in cells. Finally, the expression level of miR-3127-5p in different HCC cell lines was determined by qRT-PCR. Results: Baicalein was able to inhibit the proliferation of Bel-7402 cells by inducing cell cycle arrest at the S and G2/M phase via up-regulating the expression of p21/CDKN1A and P27/CDKN1B and suppressing the PI3K/Akt pathway. Baicalein could alter the miRNA expression profiles in Bel-7402 cells. Putative target genes for differentially expressed miRNAs could be enriched in terms of cell proliferation regulation, cell cycle arrest and were mainly involved in MAPK, PI3K-Akt, Wnt, Hippo and mTOR signaling pathways. MiR- 3127-5p, one of up-regulated miRNAs, exhibits low expression level in several HCC cell lines and its overexpression could inhibit cell growth of Bel-7402 and Hep3B cell lines by inducing S phase arrest by up-regulating the expression of p21and P27 and repressing the PI3K/Akt pathway. Conclusions: Modulation of miRNA expression may be an important mechanism underlying the anti-hepatoma effects of baicalein.

scholarly journals Perturbed functional networks in Alzheimer’s Disease reveal opposing roles for TGIF and EGR3

2018 ◽  
Author(s):  
Saranya Canchi ◽  
Balaji Raao ◽  
Deborah Masliah ◽  
Sara Brin Rosenthal ◽  
Roman Sasik ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Brain Tissue ◽  
Protein Interactions ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Large Set ◽  
Tissue Samples ◽  
Vesicle Cycle

AbstractWhile Alzheimer’s disease (AD) is the most prevalent cause of dementia, complex combinations of the underlying pathologies have led to evolved concepts in clinical and neuropathological criteria in the past decade. Pathological AD can be decomposed into subsets of individuals with significantly different antemortem cognitive decline rates. Using transcriptome as a proxy for functional state, we preselected 414 expression profiles of clinically and neuropathologically confirmed AD subjects and age matched non-demented controls sampled from a large community based neuropathological study. By combining brain tissue specific protein interactome with gene network, we identify functionally distinct composite clusters of genes which reveal extensive changes in expression levels in AD. The average global expression for clusters corresponding to synaptic transmission, metabolism, cell cycle, survival and immune response were downregulated while the upregulated cluster had a large set of uncharacterized pathways and processes that may constitute an AD specific phenotypic signature. We identified four master regulators across all clusters of differentially expressed genes by enrichment analysis includingTGIF1andEGR3.These transcription factors have previously not been associated with AD and were validated in brain tissue samples from an independent AD cohort. We identifyTGIF1,a transcriptional repressor as being neuroprotective in AD by activating co-repressors regulating genes critical for DNA repair, maintaining homeostasis and arresting cell cycle. In addition, we show that loss ofEGR3regulation, mediates synaptic deficits by targeting the synaptic vesicle cycle. Collectively, our results highlight the utility of integrating protein interactions with gene perturbations to generate a comprehensive framework for characterizing the alterations in molecular network as applied to AD.

scholarly journals Renal Tissue miRNA Expression Profiles in ANCA-Associated Vasculitis—A Comparative Analysis

2021 ◽  
Vol 23 (1) ◽  
pp. 105
Author(s):  
Matic Bošnjak ◽  
Željka Večerić-Haler ◽  
Emanuela Boštjančič ◽  
Nika Kojc
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Renal Tissue ◽  
Differentially Expressed ◽  
Tissue Samples ◽  
Anca Associated Vasculitis ◽  
Mirna Expression Profiles ◽  
Differentially Expressed Mirnas

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises autoimmune disease entities that cause target organ damage due to relapsing-remitting small vessel necrotizing vasculitis, and which affects various vascular beds. The pathogenesis of AAV is incompletely understood, which translates to considerable disease- and treatment-related morbidity and mortality. Recent advances have implicated microRNAs (miRNAs) in AAV; however, their accurate characterization in renal tissue is lacking. The goal of this study was to identify the intrarenal miRNA expression profile in AAV relative to healthy, non-inflammatory and inflammatory controls to identify candidate-specific miRNAs. Formalin-fixed, paraffin-embedded renal biopsy tissue samples from 85 patients were obtained. Comprehensive miRNA expression profiles were performed using panels with 752 miRNAs and revealed 17 miRNA that differentiated AAV from both controls. Identified miRNAs were annotated to characterize their involvement in pathways and to define their targets. A considerable subset of differentially expressed miRNAs was related to macrophage and lymphocyte polarization and cytokines previously deemed important in AAV pathogenesis, lending credence to the obtained results. Interestingly, several members of the miR-30 family were detected. However, a validation study of these differentially expressed miRNAs in an independent, larger sample cohort is needed to establish their potential diagnostic utility.

scholarly journals Data analysis of high-throughput sequencing and microarray to identify key signatures of microribonucleic acids in glioblastoma

2021 ◽  
Vol 8 (3) ◽  
pp. 21-33
Author(s):  
A. A. Pushkin ◽  
E. A. Dzenkova ◽  
N. N. Timoshkina ◽  
D. Yu. Gvaldin
Keyword(s):  
Mirna Expression ◽  
High Throughput Sequencing ◽  
Patient Survival ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Differential Expression Analysis ◽  
The Cancer Genome Atlas ◽  
Normal Brain ◽  
Sequencing Data ◽  
Tissue Samples

Purpose of the study. This research was devoted to study of mRNA and miRNA expression patterns in glioglastomas using The Cancer Genome Atlas (TCGA) data, to search for genetic determinants that determine the prognosis of patient survival and to create of interaction networks for glioblastomas.Materials and methods. Based on the data of the open TCGA database groups of glioblastomas and conventionally normal brain tissue samples were formed. Survival gene and miRNA expression data were extracted for each sample. After the data stratification by groups the differential expression analysis and search the genes affecting patient survival was carried out. The enrichment analysis by functional affiliation and an interactome analysis were performed.Results. A total of 156 glioblastoma samples with mRNA sequencing data, 571 samples with microarray microRNA analysis data, and 15 control samples were analyzed. Networks of mRNA-miRNA interactions were built and expression profiles of genes and miRNAs characteristic of glioblastomas were developed. We have determined the genes which aberrant level is associated with survival and shown the pairwise DEG and DE of microRNA correlations.Conclusion. The microRNA-mRNA regulatory pairs identified for glioblastomas can stimulate the development of new therapeutic approaches based on subtype-specific regulatory mechanisms of oncogenesis.

scholarly journals Exploring the miRNA-mRNA Regulatory Network in Clear Cell Renal Cell Carcinomas by Next-Generation Sequencing Expression Profiles

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Sören Müller ◽  
Katharina Nowak
Keyword(s):  
Mirna Expression ◽  
Renal Cell ◽  
Messenger Rna ◽  
Clear Cell ◽  
Expression Profiles ◽  
Independent Study ◽  
Differentially Expressed ◽  
Small Rna Sequencing ◽  
Renal Cell Carcinomas ◽  
Tissue Samples

Altered microRNA (miRNA) expression is a hallmark of many cancer types. The combined analysis of miRNA and messenger RNA (mRNA) expression profiles is crucial to identifying links between deregulated miRNAs and oncogenic pathways. Therefore, we investigated the small non-coding (snc) transcriptomes of nine clear cell renal cell carcinomas (ccRCCs) and adjacent normal tissues for alterations in miRNA expression using a publicly available small RNA-Sequencing (sRNA-Seq) raw-dataset. We constructed a network of deregulated miRNAs and a set of differentially expressed genes publicly available from an independent study toin silicodetermine miRNAs that contribute to clear cell renal cell carcinogenesis. From a total of 1,672 sncRNAs, 61 were differentially expressed across all ccRCC tissue samples. Several with known implications in ccRCC development, like the upregulated miR-21-5p, miR-142-5p, as well as the downregulated miR-106a-5p, miR-135a-5p, or miR-206. Additionally, novel promising candidates like miR-3065, whichi.a.targetsNRP2andFLT1, were detected in this study. Interaction network analysis revealed pivotal roles for miR-106a-5p, whose loss might contribute to the upregulation of 49 target mRNAs, miR-135a-5p (32 targets), miR-206 (28 targets), miR-363-3p (22 targets), and miR-216b (13 targets). Among these targets are the angiogenesis, metastasis, and motility promoting oncogenesc-MET,VEGFA,NRP2, andFLT1, the latter two coding for VEGFA receptors.

Long-Term Arsenic Trioxide (ATO) Treatment Changes Multiple Myeloma (MM) Cells Micro-RNA and RNA Expression Profiles

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5168-5168
Author(s):  
Jianguo Wen ◽  
Yongdong Feng ◽  
Douglas J Ballon ◽  
Chung-Che Chang
Keyword(s):  
Multiple Myeloma ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Micro Rna ◽  
Mirna Array ◽  
Mirna Expression Profiles ◽  
Oligonucleotide Microarray Analysis ◽  
High Level ◽  
Resistant Cells

Abstract Although the preliminary results of treating refractory and relapsed multiple myeloma patents with ATO are promising, the data suggest that the resistance to ATO treatment frequently occurs (57 to 79%). We treated MM cells RPMI8226 with long-term low dosage ATO (0.5 μM) and harvested the ATO resistant cells. ATO resistant cells IC50 is 4 times higher and ATO resistant cells formed 2 times more colonies with 0.75 μM ATO treatment than parental RPMI8226. P-p38 MAPK, Bcl-2, XIAP and survivin were elevated to a relatively high level in ATO resistant cells under continuous ATO stress. We have established a custom designed miRNA microarray printed with a comprehensive panel of miRNAs in miRBase version 9.0 (238 mmu-mirs) and miRNA predictions including 2617 MED-MIR predictions, 321 ‘Cand” predictions discovered through a strategy based on pylogenetice-shadowing, 129 ‘MIR” predictions discovered through a search for miRNA targets in 3′ UTR sequences. We used this miRNA array to probe the miRNA expression profiles of RPMI8226 and resistant cells and observed differences in miRNA expression between the two lines. We also performed oligonucleotide microarray analysis using HG-U133 plus 2.0 array to screen the differential gene expression. Results showed that ATO resistant cells repressed the expression of has-miR-181a, has-miR-181b, has-let-7i, has-miR-19b, has-miR-18a, has-miR-20a and has-miR222. On the other hand, LMAN1, NPGPx, HSP73 and EIF1 genes expression were up-regulated. These data revealed the preliminary mechanism how MM cells adapt to ATO and provide potential targets to overcome the ATO in MM therapy.

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