MiRNA regulation of T cell exhaustion in cutaneous T cell lymphoma [CTCL_miRNA]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE181118 | GEO | 2021/12/07
REPOSITORIES: GEO
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Project description:Cobomarsen (MRG‐106), an oligonucleotide inhibitor of miR‐155, has been evaluated in a clinical phase 1/2 trial for CTCL. We used lesional skin samples from 6 CTCL patients to identify the critical pathways affected by miR‐155 inhibition in CTCL.
2021-08-04 | GSE181117 | GEO
Project description:Cutaneous T-cell lymphomas (CTCL) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult due to a clinical and histological resemblance to benign inflammatory skin diseases. To address if microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we study miRNA expression in 199 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays we show that the most induced- (miR-326, miR-663b, miR-711) and repressed- (miR-203, miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Q-RT-PCR analysis of 104 patients with CTCL and benign skin disorders validates differential expression of 4 out of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A q-RT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity, sensitivity, and a classification accuracy of 95% indicating that miRNAs have a high diagnostic potential in CTCL.
2011-11-22 | GSE31408 | GEO
Project description:The set of expressed microRNAs in a given cell type, or “miRNome”, can be explored under many different aspects. Many studies report modulations of the miRNome in a wide variety of cancers. Papillary thyroid cancer is the most prevalent type of endocrine cancer. The presence of nodal metastases increases the risk of recurrence and mortality. In our study, we performed microRNA deep sequencing (miRSeq) of 3 PTC, their matching normal tissues and nodal metastases and designed a new bioinformatic framework to analyze variations of the different aspects of the miRNome: expression profile, isomiRs and non-templated additions distributions, mutation or A-to-I RNA-editing. Furthermore, we validated our results using qRT-PCR on independent samples from 14 patients and using the collection of miRSeq data from The Cancer Genome Atlas (up to 495 miRseq of PTC). We gave a particular attention to cell content and contamination. We showed that microRNA expression profiles of thyrocytes are altered during tumorigenesis. These alterations involve known up regulations of microRNAs such as miR-146b-5p or miR-22-3p but also down regulations such as miR-7-5p, miR-7-2-5p, miR-1179 or miR-204-5p. Furthermore, some expression modulations were increased following the nodal metastatic process such as miR-7-2-3p or miR-138-1-3p. However, we did not find variations in the other aspects of the miRNome analyzed. We used our bioinformatic frameworks on the largest PTC miRSeq data collection available, to our knowledge. It allowed us, in one study on the different aspects of the miRNome, to find modulated microRNAs that could act as biomarkers of PTC.
2015-12-01 | GSE57780 | GEO
Project description:Cutaneous T-cell lymphomas (CTCL) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult due to a clinical and histological resemblance to benign inflammatory skin diseases. To address if microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we study miRNA expression in 199 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays we show that the most induced- (miR-326, miR-663b, miR-711) and repressed- (miR-203, miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Q-RT-PCR analysis of 104 patients with CTCL and benign skin disorders validates differential expression of 4 out of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A q-RT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity, sensitivity, and a classification accuracy of 95% indicating that miRNAs have a high diagnostic potential in CTCL. miRNA microarray. From each sample 100 ng of total RNA was labeled with Hy3 fluorescent dye using the miRCURY LNA Array power labeling kit (Exiqon, Denmark). All samples were labeled the same day with the same master mix, in order to minimize technical variation. The Hy3-labelled samples were hybridized to miRCURY LNA arrays (v11.0) (Exiqon, Denmark), containing capture probes targeting all human miRNAs registered in the miRBASE version 15.0 at the Sanger Institute. The hybridization was performed overnight at 56°C according to manufacturer specifications using a Tecan HS4800 hybridization station (Tecan, Austria). Since it was not possible to hybridize all arrays in one go, samples were randomly split into 5 batches as to minimize day to day variation in the hybridization process. After hybridization the microarray slides were scanned using an Agilent G2565BA Microarray Scanner System (Agilent Technologies, Inc., USA) at 5µm resolution, and the resulting TIFF images were analyzed using the ImaGene 8.0 software on standard settings (BioDiscovery, Inc., USA).
2011-11-22 | E-GEOD-31408 | biostudies-arrayexpress
Project description:This study investigated the microRNA (miRNA) expression profiles in normal skin samples from the Uyghur and Han populations in Xinjiang and analyzed the miRNA expression differences between the two populations. The 7th generation miRCURYTM LNA Array kit (containing 3100 probes) was used to detect the miRNA expression in 10 Uyghur and 10 Han normal skin samples and to compare the miRNA expression differences between the two populations. A total of 2041 miRNAs were present in normal Uyghur and Han skin samples. In particular, 2039 miRNAs were present in normal Uyghur skin, of which 295 miRNAs were expressed more than 2.0-fold and 1461 miRNAs were expressed less than 0.5-fold of the average value. Moreover, 2041 miRNAs were expressed in normal Han skin, of which 279 miRNAs were expressed more than 2.0-fold and 1414 miRNAs were expressed less than 0.5-fold of the average value. Considering both populations together, 228 miRNAs were expressed more than 2.0-fold and 1353 miRNAs were expressed less than 0.5-fold of the average value. In the Han population, 76 miRNAs were upregulated and 171 miRNAs were downregulated compared with the Uyghur population (p < 0.05). A total of 13 miRNAs had fold changes that were greater than 10, and 9 miRNAs had fold changes that were between 3 and 10. The upregulated miRNAs were miR-1, miR-106b-5p, miR-1915-5p, miR-200c-3p, miR-221-3p, miR-222-3p, miR-3139, miR-4802-3p, miR-507, miR-541-3p, miR-876-3p, and kshv-miR-K12-2-5p. The downregulated miRNAs were miR-1207-3p, miR-206, miR-2116-5p, miR-3667-5p, miR-374b-3p, miR-4423-5p, miR-4450, miR-4468, miR-542-3p, miR-548ao-3p, and miR-553. Specific miRNA expression patterns were observed in normal Uyghur and Han skin samples, and the miRNA expression patterns differed significantly between the two populations.
2014-10-16 | GSE62354 | GEO
Project description:Friedreich’s ataxia (FRDA; OMIM 229300), an autosomal recessive neurodegenerative mitochondrial disease, is the most prevalent hereditary ataxia. In addition, FRDA patients showed additional non-neurological features such as scoliosis, diabetes and cardiac complications. Hypertrophic cardiomyopathy, which is found in two thirds of patients at the time of diagnosis, is the primary cause of death in these patients. In this data set, using small RNA-sequencing of small RNA purified from plasma samples of FRDA patients and controls we identified differential expression of miRNAs (hsa-miR-128-3p, hsa-miR-625-3p, hsa-miR-130b-5p, hsa-miR-151a-5p, hsa-miR-330-3p, hsa-miR-323a-3p, and hsa-miR-142-3p) between both groups. In addition, we found that miR-323a-3p can be used as a biomarker for differentiation of FRDA patients with cardiac problems. Identification of miRNA signatures could therefore provide new molecular explanation for pathological mechanisms occurring during the natural history of the FRDA. Since miRNA levels change with disease progression and pharmacological interventions, miRNAs will contribute to design new therapeutic strategies and improve clinical decisions. Plama miRNA profiles of 25 Friedreich's ataxia patients and 17 healthy subjects were generated by deep sequencing using Illumina HiScan SQ.
2017-10-18 | E-GEOD-105052 | biostudies-arrayexpress
Project description:In the present study we analyzed miRNA and mRNA expression profiles in human peripheral blood lymphocytes (PBLs) incubated in microgravity condition, simulated by a ground-based Rotating Wall Vessel (RWV) bioreactor. Our results show that 42 miRNAs were differentially expressed in MMG-incubated PBLs compared with 1g-incubated ones. Among these, miR-9-5p, miR-9-3p, miR-155-5p, miR-150-3p, and miR-378-3p were the most dysregulated. To improve the detection of functional miRNA-mRNA pairs we performed gene expression profiles on the same samples assayed for miRNA profiling and we integrated miRNA and mRNA expression data. The functional classification of miRNA-correlated genes evidenced significant enrichments in the biological processes of immune/inflammatory response, signal transduction, regulation of response to stress, regulation of programmed cell death and regulation of cell proliferation. We identified the correlation between miR-9-3p, miR-155-5p, miR-150-3p and miR-378-3p expression with that of genes involved in immune/inflammatory response (eg. IFNG and IL17F), apoptosis (eg. PDCD4 and PTEN) and cell proliferation (eg. NKX3-1 and GADD45A). Experimental assays of cell viability and apoptosis induction validated the results obtained by bioinformatics analyses demonstrating that in human PBLs the exposure to reduced gravitational force increases the frequency of apoptosis and decreases cell proliferation. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-07-17 | E-GEOD-57418 | biostudies-arrayexpress
Project description:Objective Circulating plasma miRNAs have been increasingly studied in the field of pituitary neuroendocrine tumor (PitNET) research. Our aim was to discover circulating plasma miRNAs species associated with growth hormone (GH) secreting PitNETs and assess how the plasma levels of discovered miRNA candidates are impacted by SSA therapy and whether there is a difference in their levels between GH secreting PitNETs and other PitNET types. Methods miRNA candidates were discovered using the whole miRNA sequencing approach and differential expression analysis. Selected miRNAs were then analyzed using real-time polymerase chain reaction (qPCR). Results Whole miRNA sequencing discovered a total of 19 differentially expressed miRNAs (DEMs) in GH secreting PitNET patients' plasma 24 hours after surgery and 19 DEMs between GH secreting PitNET patients’ plasma and non-functioning (NF) PitNET patients’ plasma. Seven miRNAs were selected for further testing of which miR-625-5p, miR-503-5p miR-181a-2-3p and miR-130b-3p showed a significant downregulation in plasma after 1 month of SSA treatment. miR-181a-5p and mir-625-5p were also found to be significantly downregulated in plasma of GH secreting PitNET patients vs. NF PitNET patients. Conclusions Our study suggests that expression of plasma miRNAs miR-625-5p, miR-503-5p miR-181a-2-3p and miR-130b-3p in GH secreting PitNETs is affected by SSA treatment. Additionally, miR-625-5p and miR-181a-5p can distinguish GH secreting PitNETs from other PitNET types warranting further research on these miRNAs for treatment efficacy.
2022-02-16 | GSE196647 | GEO
Project description:Cutaneous squamous cell carcinoma (cSCC) is the second most commonly diagnosed cancer in the United States each year. Despite a generally good prognosis, metastatic cSCC results in over 3500 deaths annually. There are no specifically targeted therapies or biomarkers for metastatic cSCC. To determine whether aberrant microRNA expression occurs in metastatic cSCC which could provide novel targets for therapy or biomarkers for earlier diagnosis or prognosis, microRNA expression profiling was performed in 48 samples including normal skin, primary tumors and metastases. Multiple microRNAs showed differential expression; miR-4286, miR-200a-3p and miR-148-3p showed increased expression and miR-1915-3p, miR-205-5p, miR-4516 and miR-150-5p showed reduced expression in metastatic samples. Several microRNAs previously showing aberrant expressionshown to be aberrantly expressed in primary cSCCs were also observed in this study including miR-100, miR-135b, miR-145, miR-21, and miR-214. In summary, several microRNAs show differential expression between primary and metastatic cSCCs; these may be useful as biomarkers for metastasis or as targets for therapytherapeutic targets. RNA extracted from primary human tissues
2015-02-28 | E-GEOD-57768 | biostudies-arrayexpress
Project description:Friedreich’s ataxia (FRDA; OMIM 229300), an autosomal recessive neurodegenerative mitochondrial disease, is the most prevalent hereditary ataxia. In addition, FRDA patients showed additional non-neurological features such as scoliosis, diabetes and cardiac complications. Hypertrophic cardiomyopathy, which is found in two thirds of patients at the time of diagnosis, is the primary cause of death in these patients. In this data set, using small RNA-sequencing of small RNA purified from plasma samples of FRDA patients and controls we identified differential expression of miRNAs (hsa-miR-128-3p, hsa-miR-625-3p, hsa-miR-130b-5p, hsa-miR-151a-5p, hsa-miR-330-3p, hsa-miR-323a-3p, and hsa-miR-142-3p) between both groups. In addition, we found that miR-323a-3p can be used as a biomarker for differentiation of FRDA patients with cardiac problems. Identification of miRNA signatures could therefore provide new molecular explanation for pathological mechanisms occurring during the natural history of the FRDA. Since miRNA levels change with disease progression and pharmacological interventions, miRNAs will contribute to design new therapeutic strategies and improve clinical decisions.
2017-10-18 | GSE105052 | GEO