Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA171389 | ENA |
REPOSITORIES: ENA
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Project description:Sirtuins (SIRT) are NAD-dependent protein deacteylases and function in cellular metabolism, stress resistance, proliferation and disease. For SIRT7, a role in ribosomal gene transcription is proposed, but its function in cancer is currently unknown. In this study, we showed that SIRT7 expression was up-regulated in a large cohort of human hepatocellular carcinoma (HCC) patients, and that high expression of SIRT7 was associated with poor prognosis of HCC patients. Notably, inactivation of SIRT7 by siRNA suppressed tumor cell growth and caused G1/S cell cycle arrest in liver cancer cells. This treatment restored p21WAF1/Cip1 activity, induced Beclin-1 and autophagic gene expression and repressed cyclin D1. To explore mechanisms in SIRT7 regulation, microRNA (miRNA) profiling was carried out. This identified five significantly down-regulated miRNAs in HCC. Bioinformatic analysis of target sites and ectopic expression in HCC cells evidenced miR-125a-5p and miR-125b to suppress SIRT7 and cyclin D1 expression and to induce p21WAF1/Cip1-dependent G1 cell cycle arrest. Furthermore, treatment of HCC cells with 5-aza-2’-deoxycytidine or ectopic expression of wild-type but not mutated p53 restored miR-125a-5p and miR-125b expression and inhibited tumor cell growth to suggest their regulation by promoter methylation and p53 activity. To evidence clinical significance of these findings, mutations in the DNA binding domain of p53 and promoter methylation of miR-125b were investigated. Four out of nine patients with induced SIRT7 carried mutations in p53 gene and one patient showed hypermethylation of miR-125b promoter region. Conclusion: Our findings suggest that oncogenic potential of SIRT in hepatocarcinogenesis and that a regulatory loop is proposed whereby SIRT7 inhibits transcriptional activation of p21WAF1/Cip1 via repression of miR-125a-5p and miR-125b. This makes SIRT7 a promising target in cancer therapy.
2012-09-30 | GSE39678 | GEO
Project description:The experimental work unveils novel targets of hsa-miR-125a-5p relevant in hepatocellular carcinoma (HCC). In particular, a genome-wide perspective of the whole miR-125a targetome has been achieved. First, two different HCC cell lines were subjected to a miRNA boosting by mimic transfections, resulting in many de-regulated genes, as observed by a transcriptomic approach. Then, the merging of down-regulated genes with results from bioinformatic predictive tools yielded a number of miR-125a direct targets candidates. Finally, those potential targets were further experimentally validated. This study could pave the way to piece together the RNA regulatory networks governed by miR-125a impacting on hepatocarcinogenesis and be exploited in the future for identifying novel biomarkers and therapeutic targets in HCC.
2025-01-27 | E-MTAB-14731 | biostudies-arrayexpress
Project description:Rationale: Currently, there are no blood-based biomarkers with clinical utility for acute ischemic stroke (IS). microRNAs (miRNAs) show promise as disease markers due to their cell-type specific expression patterns and stability in peripheral blood. Objective: To identify circulating miRNAs associated with acute IS, determine their temporal course up to 90 days post-stroke, and explore their utility as an early diagnostic marker. Methods and Results: We used RNA sequencing to study expression changes of circulating miRNAs in a discovery sample of 20 IS patients and 20 matched healthy control subjects (HCs). We further applied qRT-PCR in independent samples for validation (40 IS patients and 40 matched controls), replication (200 IS patients, 100 HCs), and in 72 patients with transient ischemic attacks (TIA). Sampling of patient plasma was done immediately upon hospital arrival. We identified, validated, and replicated three differentially expressed miRNAs, which were upregulated in IS patients compared to both HCs (miR-125a-5p [1.8-fold; P=1.5x10-6], miR-125b-5p [2.5-fold; P=5.6x10-6], and miR-143-3p [4.8-fold; P=7.8x10-9]) and TIA patients (miR-125a-5p: P=0.003, miR-125b-5p: P=0.003, miR-143-3p: P=0.005). Longitudinal analysis of expression levels up to 90 days after stroke revealed a normalization to control levels for miR-125b-5p and miR-143-3p starting at day two, while miR-125a-5p remained elevated. Levels of all three miRNAs depended on platelet numbers in a platelet spike-in experiment, but were unaffected by chemical hypoxia in N2a cells and in experimental stroke models. In a random forest classification, miR-125a-5p, miR-125b-5p and miR-143-3p differentiated between HCs and IS patients with an area under the curve (AUC) of 0.90 (sensitivity: 85.6%; specificity: 76.3%), which was superior to multimodal cranial computed tomography obtained for routine diagnostics (sensitivity: 72.5%) and previously reported biomarkers of acute IS (neuron specific enolase: AUC=0.69, interleukin 6: AUC=0.82). Conclusions: A set of circulating miRNAs (miR-125a-5p, miR-125b-5p, miR-143-3p) associates with acute IS and might have clinical utility as an early diagnostic marker.
2018-02-22 | GSE110993 | GEO
Project description:Post-transcriptional regulation of gene expression by miRNAs likely makes significant contributions to mRNA abundance at the embryo-maternal interface. In this study, we investigated how miR-26a-5p and miR-125b-5p contribute to molecular changes occurring in the uterine luminal epithelium, which serves as the first site of signal exchange between the mother and developing embryo. To measure de novo protein synthesis after miRNA delivery to primary uterine luminal epithelial cells, we employed pulsed stable isotope labeling by amino acids (pSILAC). We found that both miRNAs alter the proteome of luminal epithelial cells, impacting numerous cellular functions, immune responses, as well as intracellular and second messenger signaling pathways. Additionally, we identified several features of miRNA-mRNA interactions that may influence the targeting efficiency of miR-26a-5p and miR-125b-5p. Overall, our study suggests a complex interaction of miR-26a-5p and miR-125b-5p with their respective targets. However, both appear to cooperatively function in modulating the cellular environment of the luminal epithelium, facilitating the morphological and molecular changes that occur during the intensive communication between the embryo and uterus at pregnancy.
2025-05-07 | PXD056243 | Pride
Project description:Hepatocellular carcinoma (HCC) remains a significant clinical challenge due to limited diagnostic and therapeutic options. Non-coding RNAs, such as microRNAs (miRNAs), play key roles in cancer biology. Our previous findings showed that miR-423-5p exerts anti-cancer effects on HCC patients treated with sorafenib by promoting autophagy. In this study, we investigated the molecular mechanisms underlying its activity by generating SNU-387 HCC cell line stably overexpressing miR-423-5p and conducting a comprehensive proteomic analysis. Mass spectrometry profiling identified 698 differentially expressed proteins (DEPs) in miR-423-5p-overexpressing cells compared to controls. Functional enrichment analysis revealed significant alterations in metabolic pathways, particularly purine/pyrimidine metabolism and gluconeogenesis. To relate these findings to clinical context, we integrated experimentally validated and predicted miR-423-5p targets with The Cancer Genome Atlas (TCGA) Liver Hepatocellular Carcinoma (LIHC) dataset. Seven candidate proteins were significantly associated with patient prognosis (log-rank p < 0.05 for both overall and disease-free survival). These targets were downregulated in our miR-423-5p model but found to be upregulated in stage III HCC tissues from TCGA data.
2025-09-29 | PXD064869 | Pride
Project description:RNA-seq identifies circulating miR-125a-5p, miR-125b-5p and miR-143-3p as potential biomarkers for acute ischemic stroke
| PRJNA435535 | ENA
Project description:miR-125b-5p is a well known miRNA already describded in several forms of cancer. miR-125b-5p is expressed in adipose tissue, adipocytes as well as their precursor cells. We aim to invest the role of miR-125b-5p in white adipocytes conversion into brite adipocytes. To get an idea about putative targets of miR-125b-5p in adipocyte conversion, we transfected miR-125b-5p mimic in human Multipotent Adipose-Derived Stem (hMADS) cells, differenciated in white adipocytes. Gene expression profiling is performed 48h after hMADSC transfection. Two-condition experiment, hMADS cells at day 16 after conversion of white adipocytes into brite adipocytes, comparison of cells transfected with a mimic miR-125b-5p to cells transfected with a negative controle. Biological replicates: 4, indepently grown and harvested. On each array, one biological replicate of mimic miR-125b-5p transfected cells was directly compared to one biological replicate of mimic negative control transfected cells (serving as reference sample). All hybridizations were repeated with reversed dye assignment (dye-swap) as technical replicates.
2016-07-01 | E-GEOD-80816 | biostudies-arrayexpress
Project description:miR-125b-5p is a well known miRNA already describded in several forms of cancer. miR-125b-5p is expressed in adipose tissue, adipocytes as well as their precursor cells. We aim to invest the role of miR-125b-5p in white adipocytes conversion into brite adipocytes. To get an idea about putative targets of miR-125b-5p in adipocyte conversion, we transfected miR-125b-5p mimic in human Multipotent Adipose-Derived Stem (hMADS) cells, differenciated in white adipocytes. Gene expression profiling is performed 48h after hMADSC transfection.
2016-07-01 | GSE80816 | GEO
Project description:Aims/hypothesis. Ectopic calcification is a typical feature of diabetic vascular disease and resembles an accelerated aging phenotype. We previously found an excess of myeloid calcifying cells (MCCs) in diabetic patients. We herein examined molecular and cellular pathways linking atherosclerotic calcification with calcification by myeloid cells in the diabetic milieu. Methods. We first examined the associations among coronary calcification, MCC levels, and mononuclear cell gene expression in a cross-sectional study of 87 type 2 diabetic patients undergoing elective coronary angiography. Then, we undertook in vitro studies on mesenchymal stem cells (MSCs) and on the THP-1 myeloid cells line to verify the causal relationships of the observed associations. Results. Coronary calcification was associated with 2.8-times higher MCC levels (p=0.037) and 50% elevated expression of the osteogenic gene RUNX2 in mononuclear cells, whereas expression of Sirtuin-7 (SIRT7) was inversely correlated with calcification. In standard differentiation assays of MSCs, SIRT7 knockdown activated the osteogenic program and worsened calcification, especially in the presence of high (20 mM) glucose. In the monocytic cell line THP-1, SIRT7 downregulation drove a pro-calcific phenotype, whereas SIRT7 overexpression prevented high-glucose induced calcification. Through the JAK/STAT pathway, high glucose induced miR-125b-5p, which in turn targeted SIRT7 in myeloid cells and was directly associated with coronary calcification. Conclusions/interpretation. We describe a new pathway elicited by high glucose trough the JAK/STAT cascade, involving regulation of SIRT7 by mir-125b-5p driving calcification by myeloid cells. This pathway is associated with coronary calcification in diabetic patients and may be a target to tackle diabetic vascular disease.
2022-01-15 | GSE193510 | GEO
Project description:SIRT7 is a member of the mammalian sirtuin family of NAD+ dependent deacylases, and interacts with RNA polymerase I and UBF to regulate rDNA transcription. Various studies in mammalian cells and human clinical data have linked SIRT7 to cancer. However studies differ as to whether SIRT7 is oncogenic or tumor suppressive. Here we analyzed SIRT7 knockout mice and found SIRT7 deficiency caused sub-Mendelian birth numbers and a reduction in body size. Moreover, at 18 month of age, roughly 60 % of the SIRT7 knockout mice develop hepatocellular carcinoma (HCC), in many cases leading to suspected metastasis. Several HCC associated genes were up-regulated in livers of mice as young as 6 months of age, particularly targets of the proto-oncogene, c- MYC. Indeed SIRT7 interacts with MYC at endogenous protein levels and also represses MYC activity. Our findings thus show that SIRT7 acts as a tumor suppressor in vivo, and may suggest novel strategies to treat liver cancer. The mRNAs from 3 replicates of mouse Wildtype liver compared to 3 replicates of mouse liver lacking SIRT7
2014-08-20 | E-GEOD-50076 | biostudies-arrayexpress