Transcription repression of miR-221 leads to p27 expression in PEL
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Dan Frampton
PROVIDER: E-GEOD-18439 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:To identify differentially expressed human and viral miRNAs across a panel of B-cell lines, including several primary effusion lymphomas (PEL). Gammaherpesvirus and host cell microRNAs (miRNAs) together modulate gene expression in normal and malignant cells. Using microRNA microarrays, we determined the expression of mature viral and host cellular miRNAs in a series of B cell tumours that include Kaposiâs Sarcoma-associated herpesvirus (KSHV) infected Primary Effusion Lymphoma (PEL) and Epstein-Barr virus (EBV) infected Burkittâs lymphoma (BL) cell lines. We show that 35 host miRNAs were constitutively expressed in all the B cell lymphomas and differences in viral miRNA expression were evident between herpesvirus positive tumour types. Furthermore, we show that in PEL, miR-221 and miR-222 expression is defective due to a lack of transcript expression rather than mutation in the miRNA encoding loci. Absence of miR-221 and miR-222 resulted in the enhanced expression of the known target gene p27 (CDKN1B) and reintroduction of miR221 in PEL reduces p27 protein expression. miRNA expression profiling of a panel of 25 B-cell line samples.
2015-12-05 | E-GEOD-18437 | biostudies-arrayexpress
Project description:1) To identify changes in gene expression upon over-expression of hsa-miR-221 in JSC1 cells. 2) To identify human miRNA targets expressed in a panel of B-cell lines. Gammaherpesvirus and host cell microRNAs (miRNAs) together modulate gene expression in normal and malignant cells. Using microRNA microarrays, we determined the expression of mature viral and host cellular miRNAs in a series of B cell tumours that include Kaposiâs Sarcoma-associated herpesvirus (KSHV) infected Primary Effusion Lymphoma (PEL) and Epstein-Barr virus (EBV) infected Burkittâs lymphoma (BL) cell lines. We show that 35 host miRNAs were constitutively expressed in all the B cell lymphomas and differences in viral miRNA expression were evident between herpesvirus positive tumour types. Furthermore, we show that in PEL, miR-221 and miR-222 expression is defective due to a lack of transcript expression rather than mutation in the miRNA encoding loci. Absence of miR-221 and miR-222 resulted in the enhanced expression of the known target gene p27 (CDKN1B) and reintroduction of miR221 in PEL reduces p27 protein expression. The dataset comes in two parts. 1) 6 JSC1 samples: 2 with miR-221 lentiviral vector, 2 without and 2 with K5 short hairpin RNA as control. 2) A panel of 14 B-cell line samples. Each of the 20 samples was Cy5 labelled and run with Cy3-labelled Stratagene reference RNA.
2015-12-05 | E-GEOD-18438 | biostudies-arrayexpress
Project description:Background: The global effect of copy number and epigenetic alterations on miRNA expression in cancer is poorly understood. In the present study, we integrate genome-wide copy number, DNA methylation and miRNA expression and identify genetic mechanisms underlying miRNA dysregulation in breast cancer. Results: We identify 70 miRNAs whose expression was associated with aberrations in copy number or methylation, or both. Among these, five miRNA families are represented. Interestingly, the members of these families are encoded on different chromosomes and are complementarily altered by gain or hypomethylation across the patients. In an independent breast cancer cohort of 123 patients, 41 of the 70 miRNAs were confirmed with respect to aberration pattern and association to expression. In vitro functional experiments were performed in breast cancer cell lines with miRNA mimics to evaluate the phenotype of the replicated miRNAs. let-7e-3p, which in tumors is found associated with hypermethylation, is shown to induce apoptosis and reduce cell viability, and low let-7e-3p expression is associated with poorer prognosis. The overexpression of three other miRNAs associated with copy number gain, miR-21-3p, miR-148b-3p and miR-151a-5p, increases proliferation of breast cancer cell lines. In addition, miR-151a-5p enhances the levels of phosphorylated AKT protein. Conclusions: Our data provide novel evidence of the mechanisms behind miRNA dysregulation in breast cancer. The study contributes to the understanding of how methylation and copy number aberrations influence miRNA expression, emphasizing miRNA functionality through redundant encoding, and suggests novel miRNAs important in breast cancer. The miRNA expression profiling of 149 breast cancer samples was performed using the 8x15k “Human miRNA Microarray Kit (V2)” with design id 019118 from Agilent (Agilent Technologies, Santa Clara, CA, USA). In brief, 100 ng total RNA was dephosphorylated, labeled and hybridized for 20 hours, following the manufacturer’s protocol. Scanning was performed on Agilent Scanner G2565A, signals were extracted using Feature Extraction v9.5 and the subsequent data processing was performed using the GeneSpring software v12.0 (Agilent Technologies). In brief, the miRNA signal intensities were log2-transformed and normalized to the 90th percentile, and miRNAs that were detected in less than 10% of the samples were excluded. This resulted in 448 unique mature miRNAs.
2013-10-24 | E-GEOD-46934 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) have important roles in gene regulation. Dysregulation of miRNAs has been associated with tumorigenesis. Recent studies suggest miR-193b is a tumor suppressor gene. In a previous study, we reported that miR-193b represses cell proliferation and regulates cyclin D1 (CCND1) in melanoma. Now we demonstrate that miR-193b regulates myeloid cell leukemia sequence 1 (Mcl-1) in melanoma cells. miRNA microarray profiling revealed the miR-193b level in malignant melanomas was significantly downregulated compared to benign nevi, while a tissue microarray demonstrated overexpression of Mcl-1 in malignant melanoma. The Mcl-1 expressions were inversely correlated with the miR-193b levels in melanoma tissue samples, suggesting a potential regulatory role of miR-193b. Overexpression of miR-193b repressed Mcl-1 in melanoma cell lines. It is well known that Mcl-1 knockdown confers cell sensitivity to ABT-737, a small molecular inhibitor of Bcl-2, Bcl-XL and Bcl-w. We found miR-193b, through repressing Mcl-1 expression, could also sensitize melanoma cells that were refractory to ABT-737. Furthermore, miR-193b directly regulates Mcl-1 by targeting the 3â untranslated region (3âUTR) of Mcl-1 mRNA. Interestingly, miR-193b may recognize sequences on the 3âUTR that do not base pair with its seed region. In conclusion, our study suggests the downregulation of miR-193b could be an early event during melanoma progression, and demonstrates miR-193b directly regulates Mcl-1 by targeting both seed and seedless sequences of the 3â UTR. 15 primary melanoma samples, 8 metastatic melanomas and 8 benign nevi samples were profiled on Agilent miRNA array platform
2010-10-30 | E-GEOD-24996 | biostudies-arrayexpress
Project description:Defects in stress responses are important contributors in many chronic conditions including cancer, cardiovascular disease, diabetes, and obesity-driven pathologies like non-alcoholic steatohepatitis (NASH). Specifically, endoplasmic reticulum (ER) stress is linked with these pathologies and control of ER stress can ameliorate tissue damage. MicroRNAs have a critical role in regulating diverse stress responses including ER stress. Here we show that miR-494-3p plays a functional role during ER stress. ER stress inducers (tunicamycin and thapsigargin) robustly increase the expression of miR-494 in vitro in an ATF6 dependent manner. Surprisingly, miR-494 pretreatment dampens the induction and magnitude of ER stress in response to tunicamycin in endothelial cells. Conversely, inhibition of miR-494 increases ER stress de novo and amplifies the effects of ER stress inducers. Using Mass Spectrometry (TMT-MS) we identified many proteins that are downregulated by both tunicamycin and miR-494 in cultured human umbilical vein endothelial cells (HUVECs). Among these, we found 6 transcripts which harbor a putative miR-494 binding site. Our data indicates that ER stress driven miR-494 may act in a feedback inhibitory loop to dampen downstream ER stress signaling. We propose that RNA-based approaches targeting miR-494 or its targets may be attractive candidates for inhibiting ER stress dependent pathologies in human disease.
2021-09-09 | PXD019992 | Pride
Project description:A growing body of literature has consolidated the important role of miRNA in a variety of biological processes, in cancer development, acting both as oncogenes and tumor suppressor genes, and in their ability to distinguish tumors according to their diagnostic and prognostic properties.To date, little is known, however, about differences in miRNA expression between KIT/PDGFRA mutant and KIT/PDGFRA WT GIST.
2016-10-03 | E-MTAB-4490 | biostudies-arrayexpress
Project description:Here, we report a systematic effort to identify pro-apoptotic mRNA targets for the EBV miR-BART miRNAs. We demonstrate that at least five of the 22 miR-BART pre-miRNAs have anti-apoptotic activity and we identify seven pro-apoptotic cellular mRNA targets, six of them novel, that contribute significantly to the observed anti-apoptotic phenotype. Together, these data represent a substantial increase in our understanding of the role of the miR-BART miRNAs in promoting EBV infection and latency. Use of deep sequencing to identify all the miRNAs expressed in C666 cells and PAR-CLIP to comprehensively profile EBV miRNA targets in C666 cells.
2015-06-16 | E-GEOD-67990 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are small non-coding RNAs that repress gene expression at the post transcriptional level via an antisense RNA-RNA interaction. Generally, miRNAs derived from snap frozen or fresh samples are used for array based profiling. Since tissues in most pathology departments are available only in formalin fixed and paraffin embedded state, we sought to evaluate the miRNA derived from formalin fixed and paraffin embedded (FFPE) samples for microarray analysis. In this study, miRNAs extracted from matched snap frozen and FFPE samples were profiled using the Agilent miRNA array platform. Each miRNA sample was hybridized to arrays containing probes interrogating 470 human miRNAs. A total of seven cases were compared in either duplicate or triplicate. Intrachip and interchip analyses demonstrated that the processes of miRNA extraction, labeling and hybridization from both frozen and FFPE samples are highly reproducible and add little variation to the results, as technical replicates showed high correlations (Kendall tau=0.722-0.853, Spearman rank correlation coefficient=0.891-0.954). Our results showed consistent high correlation between matched frozen and FFPE samples (Kendall tau=0.669-0.815, Spearman rank correlation coefficient=0.847-0.948), supporting the use of FFPE-derived miRNAs for profiling. Keywords: formalin-fixed and paraffin-embedded (FFPE) miRNA profiling 7 matched frozen and FFPE lymphoid hyperplasia tissues were profiled and compared. Triplicate arrays were performed for two pairs of hyperplasia samples and duplicate arrays for three pairs of hyperplasia samples.
2010-05-17 | E-GEOD-12458 | biostudies-arrayexpress
Project description:MicroRNAs are a family of 19- to 25-nucleotides noncoding small RNAs that primarily function as gene regulators. Aberrant microRNA expression has been described for several human malignancies, and this new class of small regulatory RNAs has both oncogenic and tumor suppressor functions. Despite this knowledge, there is little information regarding microRNAs in blood especially because microRNAs in blood, if exist, were thought to be digested by RNase. Recent studies, however, have revealed that microRNAs exist and escape digestion in serum and plasma. Thus, we performed microRNA microaray to obtain insight into microRNA deregulation in the plasma of a leukemia patient. Here, we have revealed that microRNA-638 (miR-638) is stably present in human plasmas, and miR-92a dramatically decreased in the plasmas of acute leukemia patients. Our data indicate that the ratio of miR-92a/miR-638 in plasma has strong potential for clinical application as a novel biomarker for detection of leukemia. Seven normal samples and two acute leukemia samples ware profiled and compared.
2010-05-16 | E-GEOD-14772 | biostudies-arrayexpress
Project description:Cutaneous melanoma is an increasingly common form of skin cancer. The molecular mechanisms regulating melanoma progression are not completely understood. We speculated that specific miRNAs may be involved in melanoma development. We compared the miRNA expression profiles of benign nevi and metastatic melanomas. Unsupervised hierarchical clustering demonstrated a distinct miRNA expression pattern in metastatic melanomas compared to nevi. We identified miRNAs that were differentially expressed in melanoma. Notably, miR-193b was significantly down-regulated in the melanoma tissue examined. Using functional studies we demonstrated that over-expression of miR-193b significantly reduced melanoma cell proliferation, and arrested cell at G1 phase. Further gene expression analysis revealed that miR-193b regulated targets involved in cell cycle. Cyclin D1 was down-regulated by miR-193b at both the mRNA and protein level. This is the first study to show that the miR-193b may reduce cell proliferation by directly repressing cyclin D1. Overall, our study suggests that miRNAs are dysregulated in metastatic melanoma, and that miR-193b may play an important role in melanoma. 8 benign nevi and 8 metastatic melanoma tissue samples were profiled by Agilent MicroRNA Microarray (V1.5).
2010-05-16 | E-GEOD-18509 | biostudies-arrayexpress