Homo sapiens
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PROVIDER: PRJNA158625 | ENA |
REPOSITORIES: ENA
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Project description:Introduction: Amplification at chromosome 8q24 is one of the most frequent genomic abnormalities in human cancers and is associated with reduced survival duration in breast and ovarian cancers. The minimal amplified region encodes c-MYC and the non-coding RNA, PVT1 including miR-1204 encoded in exon 1b. Here we analyzed the genomic changes at chromosome 8q24.21 in breast cancer and the functional roles of miR-1204 in breast and ovarian cancer progression. Methods: The genomic changes at chromosome 8q24.21 were detected in 997 breast cancer tumors and 40 breast cancer cell lines. Expression of miR-1204 in breast and ovarian cancer cell lines was investigated by qRT-PCR method. The role of miR-1204 in the tumorigenesis of breast and ovarian cancer was explored using both knockdown and overexpression of miR-1204 in vitro. Candidate miR-1204 target genes from two independent expression microarray datasets and computational predict programs were identified and further validated by qRT-PCR and western blot methods. The role of inhibition of miR-1204 on tamoxifen sensitivity in breast cancer cells was also investigated. Results: MiR-1204 is frequently co-amplified with MYC and expression of miR-1204 is strongly correlated with the expression and amplification of the noncoding PVT1 transcript and less so with MYC in human breast and ovarian cancer cells. Inhibition of miR-1204 decreases cell proliferation and increased apoptosis in breast and ovarian cancer cell lines with 8q24 amplification, but not in lines without amplification and so may be involved in Myc-induced apoptosis. Additionally, overexpression of miR-1204 enhances both breast and ovarian cancer cell growth and Myc-initiated Rat1A cell transformation. Computational and experimental analyses 30 promising candidate miR-1204 target genes. mRNA levels for these genes were assessed after over expression and knockdown of miR-1204 as were protein levels for 10 genes for which antibodies were available. These studies implicated VDR and ESR1 as miR-1204 targets. Inhibition of miR-1204 increased response to tamoxifen in Estrogen Receptor negative breast cancer cell lines. Conclusions: We conclude that amplification of miR-1204 contributes to breast and ovarian pathophysiology at least in part, by increasing proliferation and down regulating apoptosis and by decreasing expression of VDR and ESR1. Seven cell line sample pairs, where samples are LNA transfected with antimiR-1204 or antimiR-1204 control
2012-04-30 | E-GEOD-37185 | biostudies-arrayexpress
Project description:Introduction: Amplification at chromosome 8q24 is one of the most frequent genomic abnormalities in human cancers and is associated with reduced survival duration in breast and ovarian cancers. The minimal amplified region encodes c-MYC and the non-coding RNA, PVT1 including miR-1204 encoded in exon 1b. Here we analyzed the genomic changes at chromosome 8q24.21 in breast cancer and the functional roles of miR-1204 in breast and ovarian cancer progression. Methods: The genomic changes at chromosome 8q24.21 were detected in 997 breast cancer tumors and 40 breast cancer cell lines. Expression of miR-1204 in breast and ovarian cancer cell lines was investigated by qRT-PCR method. The role of miR-1204 in the tumorigenesis of breast and ovarian cancer was explored using both knockdown and overexpression of miR-1204 in vitro. Candidate miR-1204 target genes from two independent expression microarray datasets and computational predict programs were identified and further validated by qRT-PCR and western blot methods. The role of inhibition of miR-1204 on tamoxifen sensitivity in breast cancer cells was also investigated. Results: MiR-1204 is frequently co-amplified with MYC and expression of miR-1204 is strongly correlated with the expression and amplification of the noncoding PVT1 transcript and less so with MYC in human breast and ovarian cancer cells. Inhibition of miR-1204 decreases cell proliferation and increased apoptosis in breast and ovarian cancer cell lines with 8q24 amplification, but not in lines without amplification and so may be involved in Myc-induced apoptosis. Additionally, overexpression of miR-1204 enhances both breast and ovarian cancer cell growth and Myc-initiated Rat1A cell transformation. Computational and experimental analyses 30 promising candidate miR-1204 target genes. mRNA levels for these genes were assessed after over expression and knockdown of miR-1204 as were protein levels for 10 genes for which antibodies were available. These studies implicated VDR and ESR1 as miR-1204 targets. Inhibition of miR-1204 increased response to tamoxifen in Estrogen Receptor negative breast cancer cell lines. Conclusions: We conclude that amplification of miR-1204 contributes to breast and ovarian pathophysiology at least in part, by increasing proliferation and down regulating apoptosis and by decreasing expression of VDR and ESR1.
2012-05-01 | GSE37185 | GEO
Project description:The development of drug resistance is still a major impediment for the successful treatment of cancer, such as advanced stage ovarian cancer, which has a 5-year survival rate of only 30%. The molecular processes that contribute to resistance have been extensively studied, however, not much is known about the role of microRNAs. We compared microRNA expression profiles of three isogenic cisplatin sensitive and resistant cell line pairs. The only microRNA that was consistently downregulated (FDR = 0.000) in all resistant cell lines was miR-634. We investigated the effects of miR-634 modulation in ovarian cancer cell lines and patient derived tumor cells. Overexpression of miR-634 gave rise to a modest G1 phase block and enhanced apoptosis. Furthermore, miR-634 resensitized resistant ovarian cancer cell lines and patient derived tumor cells to cisplatin chemotherapy. Similarly, miR-634 enhanced the response of tumor cells to carboplatin and doxorubicin, but not to paclitaxel. We showed that miR-634 regulates cyclin D1 (CCND1), which is required for the G1-S phase transition, explaining the effects on the cell cycle. In addition, miR-634 repressed expression of GRB2, ERK2, RSK1 and RSK2, components of the Ras-MAPK pathway. Altogether, our findings suggest that miR-634 modulates several cancer relevant targets and therefore miR-634 is an attractive therapeutic candidate to resensitize chemotherapy resistant ovarian tumors. The miRNA expression profile was determined of three cisplatin sensitive/resistant cell line pairs (ovarian cancer cell line pair A2780/A2780 DDP; colon cancer cell line pair HCT8/HCT8 DDP; bladder cancer cell line pairT24/T24 DDP10).
2014-02-04 | E-GEOD-54665 | biostudies-arrayexpress
Project description:Omentum conditioned medium (OCM) is known to enhance ovarian cancer oncogenesis. In this study, miR-33b exerts tumor suppressive effects on ovarian cancer cells in response to omentum conditioned medium (OCM) treatment. To identify the molecular mechanism and main biological pathways involved in the tumor inhibiting activity by miR-33b in the ovarian cancer metastasis. To achieve this, miR-33b was stably overexpressed in ovarian cancer cell line ES-2, and the protein expression profile of miR-33b overexpressing ES-2 cells upon OCM treatment was determined.
2022-02-17 | PXD026901 | Pride
Project description:The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 subjects were recruited for screening of differentially expressed plasma microRNAs. We found that miR-1204 was significantly increased in both plasma and aorta of elder patients with AAD, and was positively correlated with age. Cell senescence induced the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induced vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. miR-1204 aggravated angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuated β-aminopropionitrile monofumarate-induced AAD formation. Mechanistically, miR-1204 directly targeted myosin light chain kinase (MYLK) to promote VSMCs to acquire senescence-associated secretory phenotype (SASP) and lose their contractile phenotype. Overexpression of MYLK reversed miR-1204-induced VSMC senescence, SASP and contractile phenotype changes, and the decrease of transforming growth factor-β signaling pathway. Our findings suggest aging aggravates AAD via miR-1204-MYLK signaling axis.
2024-04-01 | PXD048658 | Pride
Project description:The development of drug resistance is still a major impediment for the successful treatment of cancer, such as advanced stage ovarian cancer, which has a 5-year survival rate of only 30%. The molecular processes that contribute to resistance have been extensively studied, however, not much is known about the role of microRNAs. We compared microRNA expression profiles of three isogenic cisplatin sensitive and resistant cell line pairs. The only microRNA that was consistently downregulated (FDR = 0.000) in all resistant cell lines was miR-634. We investigated the effects of miR-634 modulation in ovarian cancer cell lines and patient derived tumor cells. Overexpression of miR-634 gave rise to a modest G1 phase block and enhanced apoptosis. Furthermore, miR-634 resensitized resistant ovarian cancer cell lines and patient derived tumor cells to cisplatin chemotherapy. Similarly, miR-634 enhanced the response of tumor cells to carboplatin and doxorubicin, but not to paclitaxel. We showed that miR-634 regulates cyclin D1 (CCND1), which is required for the G1-S phase transition, explaining the effects on the cell cycle. In addition, miR-634 repressed expression of GRB2, ERK2, RSK1 and RSK2, components of the Ras-MAPK pathway. Altogether, our findings suggest that miR-634 modulates several cancer relevant targets and therefore miR-634 is an attractive therapeutic candidate to resensitize chemotherapy resistant ovarian tumors.
2014-02-04 | GSE54665 | GEO
Project description:The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 subjects were recruited for screening of differentially expressed plasma microRNAs. We found that miR-1204 was significantly increased in both plasma and aorta of elder patients with AAD, and was positively correlated with age. Cell senescence induced the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induced vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. miR-1204 aggravated angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuated β-aminopropionitrile monofumarate-induced AAD formation. Mechanistically, miR-1204 directly targeted myosin light chain kinase (MYLK) to promote VSMCs to acquire senescence-associated secretory phenotype (SASP) and lose their contractile phenotype. Overexpression of MYLK reversed miR-1204-induced VSMC senescence, SASP and contractile phenotype changes, and the decrease of transforming growth factor-β signaling pathway. Our findings suggest aging aggravates AAD via 75 miR-1204-MYLK signaling axis.
2024-04-02 | GSE253747 | GEO
Project description:Dysregulation of miRNA expression is associated with multiple diseases, including cancers where they can have oncogenic or tumor suppressive function. Here we investigated the potential tumor suppressive function of miR-450a, one of the most significantly downregulated miRNAs in ovarian cancer. RNAseq analysis revealed multipe genes involved in the epithelial-to-mesenchymal transition (EMT) were suppressed by miR-450a overexpression ovarian cancer cell line A2780. Consistently, miR-450a overexpression reduced tumor migration, invasion and increased anoikis in A2780 and SKOV-3 cell lines and reduced tumor growth in ovarian xenographic model. Combining AGO-PAR-CLIP and RNAseq analysis, we identified a panel of potential miR-450a targets of which many, including TIMMDC1, MT-ND2, ACO2 and ATP5B, regulate energetic metabolism. miR-450a expression indeed decreased mitochondrial membrane potential but increased glucose uptake and viability after glutamine withdrawal, characteristics of less invasive ovarian cancer cell lines, which are also less dependent on glutamine. In summary, we propose in this work that miR-450a acts as a tumor suppressor in ovarian cancer cells by modulating targets associated with glutaminolysis, which would lead to a decrease in the production of lipids, amino acids and nucleic acids, and also inhibition of signaling pathways associated with EMT
2019-04-30 | GSE129076 | GEO
Project description:The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. We found that miR-1204 was significantly increased in both plasma and aorta of elder patients with AAD, and was positively correlated with age. Cell senescence induced the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induced vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop.
2024-04-02 | GSE255157 | GEO
Project description:Breast cancer cells and two metaplastic breast cancer cell lines were used: a widely available, HS578T, and a novel line isolated from a metaplastic breast cancer tumor, BAS. Doxorubicin and paclitaxel resistant derivatives of these metaplastic lines were generated and miR profiling performed.
2023-01-29 | GSE144445 | GEO