Epigenetic downregulation of hsa-miR-193b-3p increases Cyclin D1 expression level and cell proliferation in human meningiomas
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PROVIDER: PRJNA1010811 | ENA |
REPOSITORIES: ENA
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Project description:Meningiomas are common intracranial tumors in adults. Abnormal miRNA expression plays a role in their pathogenesis. Change in miRNA expression level can be caused by impaired epigenetic regulation of miRNA-encoding genes. We found genomic region covering MIR193B gene as DNA hypermethylated in meningiomas based on analysis of genome-wide methylation (HM450k Illumina arrays). Hypermethylation of MIR193B was as also confirmed by bisulfite pyrosequencing. Both hsa-miR-193b-3p and hsa-miR-193b-5p are downregulated in meningiomas as found with qRT-PCR. Lower expression of hsa-miR-193b-3p and higher MIR193b methylation was observed in WHO GII/GIII as compared to GI meningiomas. 3’UTR of CCND1 mRNA was identified as target of hsa-miR-193b-3p as further validated with luciferase reporter assay in IOMM-Lee meningioma cells. IOMM-Lee cells transfected with hsa-miR-193b-3p mimic showed decreased cyclin D1 level and lower cell viability and proliferation, confirming suppressive nature of this miRNA. Cyclin D1 protein expression (immunoreactivity) was higher in atypical than in benign meningiomas, accordingly to observation of lower hsa-miR-193b-3p level in GII tumors. The commonly observed hypermethylation of MIR193B in meningiomas apparently contributes to downregulation of hsa-miR-193b-3p. Since hsa-miR-193b-3p regulates proliferation of meningioma cells through negative regulation of cyclin D1 expression, it seems to be an important tumor suppressor in meningiomas.
2023-09-04 | GSE241956 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE18509: miR-193b represses cell proliferation and regulates cyclin D1 in melanoma: benign nevi and metastatic melanoma GSE18510: miR-193b represses cell proliferation and regulates cyclin D1 in melanoma: Malme-3M Refer to individual Series
2010-05-16 | E-GEOD-18512 | biostudies-arrayexpress
Project description:Meningiomas are common intracranial tumors in adults. Abnormal microRNA (miRNA) expression plays a role in their pathogenesis. Change in miRNA expression level can be caused by impaired epigenetic regulation of miRNA-encoding genes. We found the genomic region covering the MIR193B gene to be DNA hypermethylated in meningiomas based on analysis of genome-wide methylation (HumanMethylation450K Illumina arrays). Hypermethylation of MIR193B was also confirmed via bisulfite pyrosequencing. Both hsa-miR-193b-3p and hsa-miR-193b-5p are downregulated in meningiomas. Lower expression of hsa-miR-193b-3p and higher MIR193B methylation was observed in World Health Organization (WHO) grade (G) II/III tumors as compared to GI meningiomas. CCND1 mRNA was identified as a target of hsa-miR-193b-3p as further validated using luciferase reporter assay in IOMM-Lee meningioma cells. IOMM-Lee cells transfected with hsa-miR-193b-3p mimic showed a decreased cyclin D1 level and lower cell viability and proliferation, confirming the suppressive nature of this miRNA. Cyclin D1 protein expression (immunoreactivity) was higher in atypical than in benign meningiomas, accordingly to observations of lower hsa-miR-193b-3p levels in GII tumors. The commonly observed hypermethylation of MIR193B in meningiomas apparently contributes to the downregulation of hsa-miR-193b-3p. Since hsa-miR-193b-3p regulates proliferation of meningioma cells through negative regulation of cyclin D1 expression, it seems to be an important tumor suppressor in meningiomas.
| S-EPMC10487813 | biostudies-literature
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.
2009-12-20 | GSE18510 | GEO
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.
2009-12-20 | GSE18509 | GEO
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
Project description:Neuroblastoma is the most common diagnosed tumor in infants and the second most common extracranial tumor of childhood. The survival rate of patients with high-risk neuroblastoma is still very low despite intensive multimodal treatments. Therefore, new treatment strategies are needed. In recent years, miRNA-based anticancer therapy has received growing attention. Advances in this novel treatment strategy strongly depends on the identification of candidate miRNAs with broad-spectrum antitumor activity. Here, we identify miR-193b as a miRNA with tumor suppressive properties. We show that miR-193b is expressed at low levels in neuroblastoma cell lines and primary tumor samples. Introduction of miR-193b mimics into nine neuroblastoma cell lines with distinct genetic characteristics significantly reduces cell growth in vitro independent of risk factors such as p53 functionality or MYCN amplification. Functionally, miR-193b induces a G1 cell cycle arrest and cell death in neuroblastoma cell lines by reducing the expression of MYCN, Cyclin D1 and MCL-1, three important oncogenes in neuroblastoma of which inhibition has shown promising results in preclinical testing. Therefore, we suggest that miR-193b may represent a new candidate for miRNA-based anticancer therapy in neuroblastoma.
| S-EPMC5915064 | biostudies-literature
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: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 3’ untranslated region (3’UTR) of Mcl-1 mRNA. Interestingly, miR-193b may recognize sequences on the 3’UTR 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 3’ UTR.
2010-10-30 | GSE24996 | GEO
Project description:Analysis of mammary glands from tet-inducible(rtTA) transgenic mice expressing cyclin D1 using Affymetrix Mouse Gene 1.0 ST GeneChip arrays. MMTV-rtTA transgenic mice (MMTV-Mouse Mammary Tumor Virus promoter) were cross-mated to cyclin D1 transgenic mice under control of tet operon. 8-week-old tetracycline-inducible cyclin D1/rtTA bi-transgenic pregnant female mice (12 days postcoitus) were treated with doxycycline through drinking water supplementation at a final concentration of 2 mg/ml. Control mice were rtTA transgenics alone and treated in the same manner. After 7 days of doxycycline treatment, the mice were sacrificed and mammary glands taken for RNA isolation. Results provide insight into the in vivo gene expression pattern regulated by cyclin D1 through acute induction. Analysis of mammary glands from MMTV-cyclin D1/WT and MMTV-cyclin D1/KE using Affymetrix Mouse 430A v2.0 GeneChip arrays. Cyclin D1 point mutant, cyclin D1/KE K112E (K112E) contains a lysine to glutamine substitution at amino acid position 112. cyclin D1. The cyclin D1/KE mutant fails to induce cyclin D1-dependent kinase activity. Female MFD1, MFD1-KE, and WT mice were monitored twice weekly, up to 760 days, for the development of palpable tumors. Those developing palpable tumors were sacrificed within a week of tumor detection. Tumors were dissected and portions snap frozen for RNA isolation. Results provide insight into the in vivo gene expression pattern regulated by cyclin D1 that is kinase independent.
2013-12-31 | GSE43216 | GEO