Global expression analysis of miR-32/455/181a/181b overexpression or PI3K knockdown in KYSE30 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Weidong Han
PROVIDER: E-GEOD-43195 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Analysis of the effect of the miRNA set (miR-32/455/181a/181b) on global gene expression. The hypothesis tested was that overexpression of these miRNAs would produce changes in gene expression similar to changes caused by PI3K knockdown. Data provided insight into genes that are disrupted with either individual miRNA and siRNA or the combination of miRNAs or siRNAs.
2012-12-29 | GSE43195 | GEO
Project description:We have identified a single miRNA, miR-181a, that can modulate TGF-β signaling to induce and maintain EMT, and effect further downstream events of tumour cell survival, altered response to chemotherapy, migration, invasion and dissemination in vivo. Our present study provides an understanding of how enhanced expression of miR-181a can confer malignant and invasive traits through the modulation of a canonical signaling pathway and a consequent maintenance of a mesenchymal state. Furthermore, inhibition of miR-181a led to a reversion of EMT and subsequent events through decreased TGF-β signaling. Our data confirmed Smad7 as a functional target through which TGF-β-mediated EMT occurs; re-expression of Smad7 lacking its 3'UTR was able to rescue miR-181a-mediated phenotypes, deeming Smad7 as a critical mediator of miR-181a-induced EMT. Other recent studies support the crucial role(s) that miRNAs play in mediating EMT and consequent aggressive disease traits. For example, the miR-106b-25 cluster has also been shown to target Smad7 and mediate TGF-β-induced EMT downstream to Six1 in breast cancer34. miR-9 directly targets E-cadherin and inhibition of miR-9 had led to an inhibition of metastasis35. Conversely, the miR-200 and -205 family was shown to target transcriptional repressors of E-cadherin, ZEB1 and SIP1, and re-expression of these miRNAs led to a mesenchymal-to-epithelial transition and prevented TGF-β -induced EMT36. A2780 ovarian cancer cell lines stably expressing either pBABE (control vector), p181a#1( clone 1 expressing miR-181a) or p181a#2( clone 2 expressing miR-181a)
2013-12-01 | E-GEOD-52077 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are expressed from a class of small non-protein coding RNA molecules. Growing evidence shows that miRNAs are potent mediators of post-transcriptional gene silencing and emerged to be critical in the regulation of innate and adaptive immune responses (Ansel KM, Immunol Rev 2013, p5; Baumjohann D, Nature Rev Immunol 2013, p666). MicroRNA-181a (miR-181a) constitutes the most prominently expressed miRNA species in DP thymocytes (Neilson JR, Genes Dev 2007, p578; Kirigin FF, JI 2012, p3257) and has been associated with modulating TCR signal strength via targeting serine/threonine as well as tyrosine phosphatases (Li Q-J, Cell 2007, p147). Consequently, elevated expression of miR-181a results in reduced phosphatase activity and increased TCR signal strength. The effect of aberrant expression of miR-181a on TCR signaling has been already analyzed employing short-term assays and in vitro organ cultures. Our group started to investigate the consequences of miR-181a/b-1 deletion on T cell development in vivo in the steady state. To this end, we developed a new mouse model - miR-181a/b-1 knockout mice (Zietara N et al, PNAS 2013b). During investigations of the immune system of miR-181a/b-1 deficient mice we discovered that these miRNAs are critical for the development of invariant natural killer (NK) T cells. Such cells are known to be selected by a high affinity agonist ligands, thus they are particularly sensitive to the modulation of TCR signaling thresholds, which is achieved by miR-181a/b-1 (Zietara N et al, PNAS 2013b). Furthermore we hypothesized that similar regulation might apply for the other T cell populations selected under high TCR signal strength, like Treg cells. Thus our current research focuses on the role of miR-181a/b-1 during Treg cell development in the thymus as well as on their function in the periphery.
2019-02-08 | GSE115391 | GEO
Project description:We have identified a single miRNA, miR-181a, that can modulate TGF-β signaling to induce and maintain EMT, and effect further downstream events of tumour cell survival, altered response to chemotherapy, migration, invasion and dissemination in vivo. Our present study provides an understanding of how enhanced expression of miR-181a can confer malignant and invasive traits through the modulation of a canonical signaling pathway and a consequent maintenance of a mesenchymal state. Furthermore, inhibition of miR-181a led to a reversion of EMT and subsequent events through decreased TGF-β signaling. Our data confirmed Smad7 as a functional target through which TGF-β-mediated EMT occurs; re-expression of Smad7 lacking its 3'UTR was able to rescue miR-181a-mediated phenotypes, deeming Smad7 as a critical mediator of miR-181a-induced EMT. Other recent studies support the crucial role(s) that miRNAs play in mediating EMT and consequent aggressive disease traits. For example, the miR-106b-25 cluster has also been shown to target Smad7 and mediate TGF-β-induced EMT downstream to Six1 in breast cancer34. miR-9 directly targets E-cadherin and inhibition of miR-9 had led to an inhibition of metastasis35. Conversely, the miR-200 and -205 family was shown to target transcriptional repressors of E-cadherin, ZEB1 and SIP1, and re-expression of these miRNAs led to a mesenchymal-to-epithelial transition and prevented TGF-β -induced EMT36.
2013-12-01 | GSE52077 | GEO
Project description:Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor associated with poor prognosis. MicroRNAs (miRNAs) play crucial regulatory roles in the cancer development. However, the role of miRNAs in OSCC development and progression is not well understood. Methods: We sought to establish a dynamic Chinese hamster OSCC animal model, construct miRNA differential expression profiles of its occurrence and development, predict its targets, and perform functional analysis and validation in vitro. Results: Using expression and functional analyses, the key candidate miRNA (miR-181a-5p) was selected for further functional research, and the expression of miR-181a-5p in OSCC tissues and cell lines was detected. Subsequently, transfection technology and a nude mouse tumorigenic model were used to explore potential molecular mechanisms. miR-181a-5p was significantly downregulated in human OSCC specimens and cell lines, and decreased miR-181a-5p expression was observed in multiple stages of the Chinese hamster OSCC animal model. Moreover, upregulated miR-181a-5p significantly inhibited OSCC cell proliferation, colony formation, invasion, and migration; blocked the cell cycle; and promoted apoptosis. BCL2 was identified as a target of miR-181a-5p. BCL2 may interact with apoptosis- (BAX), invasion- and migration- (TIMP1, MMP2, and MMP9), and cell cycle-related genes (KI67, E2F1, CYCLIND1, and CDK6) to further regulate biological behavior. Tumor xenograft analysis indicated that tumor growth was significantly inhibited in the high miR-181a-5p expression group. Conclusions: Our findings indicate that miR-181a-5p can be used as a potential biomarker and provide a novel animal model for mechanistic research on oral cancer.
2023-01-10 | GSE222429 | GEO
Project description:The molecular mechanism responsible for Ewing Sarcoma (ES) remains largely unknown. This study compared global miRNA expression in biopsies from 20 ES patients, affected by primary untreated tumors, with miRNA expressed in normal human mesenchymal stromal cells (MSCs) by microarray analysis. A miRTarBase database was used to identify the predicted target genes for differentially-expressed miRNAs. The miRNAs microarray analysis revealed distinct patterns of miRNA expression between ES biopsies and normal MSCs. 58 of the 954 analyzed miRNAs were significantly differentially expressed in ES samples compared to MSCs. Moreover, the qRT-PCR analysis, carried out on three selected miRNAs, showed that miR-181b, miR-1915 and miR-1275 were significantly aberrantly-regulated, confirming the microarray results. Bio-database analysis identified BCL-2 as a bona fide target gene of the miR-21, miR-181a, miR-181b, miR-29a, miR-29b, miR-497, miR-195, miR-Let-7a, miR-34a. Using paraffin-embedded tissues from ES, this study has identified several potential target miRNAs and one gene that might be considered novel critical biomarkers for ES pathogenesis.
2016-12-26 | GSE80201 | GEO
Project description:The generation of highly-reactive T lymphocytes against tumor-associated antigens remains an obstacle for effective adoptive immunotherapy of cancer. Recently, we found that microRNA-181a (miR-181a) acts as an intrinsic modulator of T cell antigen sensitivity in a transgenic T cell line in vitro. This molecule is part of a growing family of evolutionarily selected small interfering RNA that control gene expression at the posttranscriptional level by targeting messenger RNA (mRNA) for degradation or translational repression. Here, we explored the use of miR-181a to improve anti-tumor T cell responsiveness against weakly immunogenic tumor-associated antigens. We found that genetic engineering of T lymphocytes with miR-181a dramatically augmented the function of poorly responsive human tumor-infiltrating lymphocytes and TCR-engineered peripheral blood lymphocytes, resulting in potent anti-tumor reactivity. Furthermore, in a mouse model, miR-181a increased the function of self/tumor-specific CD8+ T cells enabling effective tumor destruction in the absence of vaccination or exogenous cytokines that were otherwise essential requirements and thus represents a significant advance over previous approaches. Although miRNAs have been previously shown to play critical functional roles in the development and function of vertebrate immune systems and pathogenesis of cancer, this report comprises the first use of a miRNA gene as tool in the treatment of disease. Keywords: cellular modification design
2008-10-01 | GSE9240 | GEO
Project description:The generation of highly-reactive T lymphocytes against tumor-associated antigens remains an obstacle for effective adoptive immunotherapy of cancer. Recently, we found that microRNA-181a (miR-181a) acts as an intrinsic modulator of T cell antigen sensitivity in a transgenic T cell line in vitro. This molecule is part of a growing family of evolutionarily selected small interfering RNA that control gene expression at the posttranscriptional level by targeting messenger RNA (mRNA) for degradation or translational repression. Here, we explored the use of miR-181a to improve anti-tumor T cell responsiveness against weakly immunogenic tumor-associated antigens. We found that genetic engineering of T lymphocytes with miR-181a dramatically augmented the function of poorly responsive human tumor-infiltrating lymphocytes and TCR-engineered peripheral blood lymphocytes, resulting in potent anti-tumor reactivity. Furthermore, in a mouse model, miR-181a increased the function of self/tumor-specific CD8+ T cells enabling effective tumor destruction in the absence of vaccination or exogenous cytokines that were otherwise essential requirements and thus represents a significant advance over previous approaches. Although miRNAs have been previously shown to play critical functional roles in the development and function of vertebrate immune systems and pathogenesis of cancer, this report comprises the first use of a miRNA gene as tool in the treatment of disease. Keywords: cellular modification design For the 6 mouse samples the Operon Array-Ready Oligo Set (AROSâ¢) V 4.0 contains 35,852 longmer probes representing 25,000 genes and about 38,000 gene transcripts and also includes 380 controls platform was used and each sample was hybridized in duplicate. For the 6 human samples, the human cDNA microarray platform was used which consist of 17 k cDNA array included a combination from a RG_HsKG_031901 7 k clone set and 10,000 clones from the RG_Hs_seq_ver_070700 40 k clone set (Research Genetics, Huntsville, AL). The cDNA clones include 12,072 uniquely named genes, 875 duplicates of named genes.
2010-05-19 | E-GEOD-9240 | biostudies-arrayexpress
Project description:Global expression analysis of miR-32/455/181a/181b overexpression or PI3K knockdown in KYSE30 cells
| PRJNA184876 | ENA
Project description:Purpose: FOLFIRINOX has become standard therapy for patients with advanced stages pancreatic ductal adenocarcinoma (PDAC). However, only a subset of patients benefits from this therapy and biomarkers to guide clinical decisions are lacking. This study aimed to discover circulating microRNAs (miRNAs) as potential stratifying and monitoring biomarkers in patients with PDAC treated with FOLFIRINOX and to investigate their functional roles. Methods: A microarray was used in plasma samples from a first cohort of 11 patients selected based on their long versus short progression-free survival (PFS) after FOLFIRINOX. Nine miRNAs were validated using RT-qPCR in an independent cohort (n=43). The best discriminative miRNA was evaluated in tumor tissue samples and associated with clinicopathological features by Cox regression analyses. In vitro studies explored its role on cell proliferation, key downstream targets, and interaction with 5-fluorouracil, irinotecan, and oxaliplatin. Results: MiR-181a-5p was validated as significantly down-regulated in non-progressive compared to progressive patients after FOLFIRINOX. In multivariate analysis, this down-regulation correlated with improved PFS and overall survival, especially combined with CA19.9 decline (log-rank p<0.001, HR=0.153, 95% C.I. 0.067–0.347 and log-rank p=0.033, HR=0.201, 95% C.I. 0.070–0.576, respectively). Overexpression of miR-181a-5p increased proliferation of PDAC cells and inversely correlated with expression of ATM. Furthermore, inhibition of miR-181a-5p coupled with oxaliplatin exposure increased DNA damage and decreased cell viability. Conclusion: Our findings endorse miR-181a-5p as a biomarker for monitoring response to FOLFIRINOX and prognostication. MiR-181a-5p inhibition can potentially enhance sensitivity to oxaliplatin by amplifying the DNA damage response and cell death.
2019-01-01 | GSE109647 | GEO