MiR-18a regulates the miRNAs by target Dicer in Nasopharyngeal carcinoma HK-1 cell.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE32680 | GEO | 2012/03/01
SECONDARY ACCESSION(S): PRJNA146913
REPOSITORIES: GEO
Similar Datasets
Project description:As the biogenesis of miRNAs depends on the cleavage by the RNase III enzyme Dicer, miR-18a may change the miRNA expression profiles by targeting dicer. We then performed the miRNA array assay to investigate the miRNA profiles change caused by miR-18a. Total RNA obtained from two pairs,one is the miR-18a overexpression cell line compared to the miRNAs (control), the other is the over-expression miR-18a cell line transfected Dicer plasmid.
2012-03-01 | E-GEOD-32680 | biostudies-arrayexpress
Project description:To search for molecular processes underlying miR-18a-mediated oncogenesis in nasopharyngeal carcinoma(NPC) cells, whole-genome mRNA microarray analysis was performed using the HumanGene Expression 4 x 44k v2 Microarray Kit (Agilent Technologies) in 6-10B cells with stable miR-18a overexpression and in 5-8F cells with transient silencing of miR-18a by siRNA. Differentially expressed genes in miR-18a-overexpressing cell and differentially expressed genes in miR-18a knockdown cells were analyzed.
2019-12-25 | GSE137689 | GEO
Project description:Using the orthotopic breast cancer xenograft model of basal-like breast cancer MDA-MB-231 line, we have found that the expression of miRNAs encoded by MIR17HG was significantly decreased in cells isolated from spontaneous lung metastases compared to cells from primary tumors grown in orthotopic sites. We investigated the role of a MIR17HG family member, miR-18a, in primary tumor growth and pulmonary metastasis from the orthotopic site. We demonstrated that enforced expression of exogenous miR-18a, significantly limited continuous growth of primary tumors in mammary gland fat pads and reduced spontaneous lung metastasis. Further investigation on the mechanism of miR-18a action led to the finding that the expression of HIF1A, a key regulator of tumor metastasis, was regulated by miR-18a. Enforced miR-18a expression significantly decreased HIF1A expression at both mRNA and protein levels, resulting in altered transcriptional response and decreased survival of cells in response to Cobalt(II) chloride (CoCl2), a hypoxia-mimicking agent. Conversely, miR-18a knockdown significantly increased HIF1A expression levels and enhanced cell survival in response to CoCl2. Analysis of expression data of human breast tumor tissues showed that miR-18a expression is inversely correlated with HIF1A expression in basal-like breast tumors, supporting a role of miR-18a in restricting HIF1A expression in this subtype of breast cancer. In addition, we demonstrated that hypoxia inhibits miR-18a expression, likely through MYC inactivation. Furthermore, gene expression and functional analysis revealed that miR-18a also plays a role in regulating cell adhesion, migration and invasion. Taken together, this study provides evidence for a novel role of miR-18a to inhibit breast cancer metastasis. Our results suggest that miR-18a downregulation might provide tumor cells survival/growth advantage under hypoxic pressure in basal-like breast cancer.
2013-07-31 | GSE45362 | GEO
Project description:Using the orthotopic breast cancer xenograft model of basal-like breast cancer MDA-MB-231 line, we have found that the expression of miRNAs encoded by MIR17HG was significantly decreased in cells isolated from spontaneous lung metastases compared to cells from primary tumors grown in orthotopic sites. We investigated the role of a MIR17HG family member, miR-18a, in primary tumor growth and pulmonary metastasis from the orthotopic site. We demonstrated that enforced expression of exogenous miR-18a, significantly limited continuous growth of primary tumors in mammary gland fat pads and reduced spontaneous lung metastasis. Further investigation on the mechanism of miR-18a action led to the finding that the expression of HIF1A, a key regulator of tumor metastasis, was regulated by miR-18a. Enforced miR-18a expression significantly decreased HIF1A expression at both mRNA and protein levels, resulting in altered transcriptional response and decreased survival of cells in response to Cobalt(II) chloride (CoCl2), a hypoxia-mimicking agent. Conversely, miR-18a knockdown significantly increased HIF1A expression levels and enhanced cell survival in response to CoCl2. Analysis of expression data of human breast tumor tissues showed that miR-18a expression is inversely correlated with HIF1A expression in basal-like breast tumors, supporting a role of miR-18a in restricting HIF1A expression in this subtype of breast cancer. In addition, we demonstrated that hypoxia inhibits miR-18a expression, likely through MYC inactivation. Furthermore, gene expression and functional analysis revealed that miR-18a also plays a role in regulating cell adhesion, migration and invasion. Taken together, this study provides evidence for a novel role of miR-18a to inhibit breast cancer metastasis. Our results suggest that miR-18a downregulation might provide tumor cells survival/growth advantage under hypoxic pressure in basal-like breast cancer. A lung metastatic subline, designated as MB231RN-LM, was derived from MDA-MB-231 breast cancer cells through in vivo selection. The MB231RN-LM cells were stably transfected with has-miR-18a or control vector and treated with 200uM Cobalt(II) chloride (CoCl2, a hypoxia-mimicking agent) for 4 hr. A total of 8 samples were subjected to microarray analysis, with two biological repeats for each experiment condition.
2013-07-31 | E-GEOD-45362 | biostudies-arrayexpress
Project description:Dicer is an RNase III-family endoribonuclease and haploinsufficient tumor suppressor that is required for the biogenesis of miRNAs, yet in vivo structure-function characterization of its RNase IIIA and IIIB domains have not been reported. In murine Dicer knockout fibroblasts, we expressed human Dicer with point mutations in the RNase III, helicase, and PAZ domains and characterized miRNA expression by Northern blot and massively parallel sequencing of small RNAs. Inactivation of the RNase IIIA or IIIB domain blocked maturation of miRNAs derived from the 3’ or 5’ arms of miRNA precursors, respectively, and resulted in altered miRNA expression profiles.
2012-07-13 | GSE36978 | GEO
Project description:Purpose The analysis of breast cancer residual tumors after neoadjuvant chemotherapy (nCT) may be useful for identifying new biomarkers. MicroRNAs are known to be involved in oncogenic pathways and treatment resistance of breast cancer. Our aim was to determine the role of miR-18a, a member of the miR-17-92a cluster, in breast cancer behavior and outcome after nCT. Methods Pre- and post-nCT tumor miR-18a expression was retrospectively assessed by qRT-PCR in 121 patients treated with nCT and was correlated with survival outcomes and with clinical and pathological characteristics. Breast cancer-derived MCF-7 and MDA-MB-231 cell lines were transfected with miR-18a and anti-miR-18a to evaluate the biological effects of this molecule. In addition, whole-transcriptome expression analysis was performed. Results High miR-18a expression in post-nCT residual tumors was found to be associated with a significantly worse overall survival [hazard ratio (HR): 2.80, 95% confidence interval (CI): 1.01–7.76] and a strong trend towards a poorer disease-free survival (HR: 2.44, 95% CI: 0.99–5.02) compared to low miR-18a expressing post-nCT residual tumors. Clinical and experimental data were found to be in conformity with the proliferative effects of miR-18a, which showed a significant correlation with Ki67 and MYBL2 expression, both in pre- and post-nCT tumors and in public databases. In vitro analysis of the role of miR-18a in breast cancer-derived cell lines showed that a high expression of miR-18a was associated with a low expression of the estrogen receptor (ER), a decreased sensitivity to tamoxifen and an enrichment in luminal B and endocrine resistance gene expression signatures. Conclusions From our data we conclude that post-nCT miR-18a expression in breast cancer serves as a negative prognostic marker, especially in luminal tumors. Clinical, in vitro and in silico data support the role of miR-18a in breast cancer cell proliferation and endocrine resistance and suggest its potential utility as a biomarker for additional adjuvant treatment in patients without a pathologic complete response to neoadjuvant therapy.
2019-05-27 | GSE102121 | GEO
Project description:Stem cell therapy requires massive scale homogeneous stem cells under strictly qualification control. However, Prolonged ex vivo expansion impairs the biological functions and results in senescence of mesenchymal stem cells (MSCs). We investigated the function of CTDSPL in premature senescence process of MSCs and clarified that miR-18a-5p played a prominent role in preventing senescence of long-term cultured MSCs and promoting the self-renew ability of MSCs. Inhibition of miR-18a-5p promoted the expression of CTDSPL and induced premature senescence of MSCs. Continuous overexpression of miR-18a-5p improved self-renewal of MSCs by reduced ROS level, increased expression of Oct4 and Nanog, promoted growth rate and differentiation capability. We reported for the first time the dynamic interaction of miR-18a-5p and CTDSPL is crucial for stem cell senescence.
2022-09-04 | GSE212185 | GEO
Project description:Dicer is an RNase III-family endoribonuclease and haploinsufficient tumor suppressor that is required for the biogenesis of miRNAs, yet in vivo structure-function characterization of its RNase IIIA and IIIB domains have not been reported. In murine Dicer knockout fibroblasts, we expressed human Dicer with point mutations in the RNase III, helicase, and PAZ domains and characterized miRNA expression by Northern blot and massively parallel sequencing of small RNAs. Inactivation of the RNase IIIA or IIIB domain blocked maturation of miRNAs derived from the 3’ or 5’ arms of miRNA precursors, respectively, and resulted in altered miRNA expression profiles. Small RNAs from murine mesenchymal stem cells (MScs) with and without Dicer (WT:Dicer f/f, KO:Dicer -/-, KO transfected with various hsDicer point mutants) were analyzed.
2012-07-13 | E-GEOD-36978 | biostudies-arrayexpress
Project description:Lung ischemia-reperfusion (IR) is known to occur after lung transplantation or cardiac bypass. IR leads to tissue inflammation and damage, is also associated with increased morbidity and mortality. Various receptors are known to partake in activation of innate immune system, but the downstream mechanism of tissue damage and inflammation is yet unknown. MicroRNAs (miRNA) are in the forefront in regulating ischemia reperfusion injury and are involved in inflammatory response. Here, we have identified by high throughput approach and evaluated distinct set of miRNAs that may play a role in response to IR in rat lung tissue. Top three differentially expressed miRNAs were validated through quantitative PCRs in the IR rat lung model and an in vitro model of IR of hypoxia and reoxygenation exposed type II alveolar cells. Among the miRNAs, miR-18a-5p showed consistent downregulation in both the model systems on IR. Cellular and molecular analysis brought to light a crucial role of this miRNA in ischemia reperfusion. MiR-18a-5p plays a role in IR mediated apoptosis, ROS production and regulates the expression of neuropeptide Galanin. It also influences the nuclear localization of transcription factor: Nuclear factor-erythroid 2 related factor (Nrf2) which in turn may regulate the expression of miR-18a gene. Thus, we have not only established a rat model for lung IR and enumerate the important miRNAs involved in IR but have also extensively characterized the role of miR-18a-5p in the same. This study will have important clinical and therapeutic implications for and during transplantation procedures.
2020-11-19 | GSE161520 | GEO
Project description:Drosophila Dicer-1 produces microRNAs (miRNAs) from pre-miRNA, whereas Dicer-2 generates small interfering RNAs (siRNAs) from long dsRNA. loquacious (loqs) encodes three Dicer partner proteins, Loqs-PA, Loqs-PB, and, Loqs-PD, generated by alternative splicing. To understand the function of each Loqs isoform, we constructed loqs isoform-specific rescue flies. Loqs-PD promotes siRNA production in vivo by Dicer-2. Loqs-PA or Loqs-PB is required for viability, but the proteins are not fully redundant: Loqs-PB is required to produce a specific subset of miRNAs. Surprisingly, Loqs-PB tunes the product size cleaved by Dicer-1 from pre-miR-307a, generating a longer miRNA isoform with a distinct seed sequence and target specificity. The mouse and human Dicer-binding partner TRBP, a homolog of Loqs-PB, similarly tunes the site of pre-miR-132 cleavage by mammalian Dicer. Thus, Dicer-binding partner proteins can change the choice of cleavage site by Dicer, producing miRNAs with different target specificities than those that would be made by Dicer alone.
2012-12-07 | GSE37443 | GEO