Target gene regulatory network of miR-497 in angiosarcoma
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ABSTRACT:
PROVIDER: PRJNA1003055 | ENA |
REPOSITORIES: ENA
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Project description:Angiosarcoma (AS) is a vascular sarcoma that is highly aggressive and metastatic. Due to its rarity, treatment options for patients are limited, therefore more research is needed to identify possible therapeutic vulnerabilities. We previously found that endothelial deletion of Dicer1 drives AS development in mice. Given the role of DICER1 in canonical microRNA (miRNA) biogenesis, this suggests that miRNA loss may be important in AS development. After testing miRNAs previously suggested to have a tumor-suppressive role in AS, microRNA-497-5p (miR-497) suppressed cell viability most significantly. We also found that miR-497 expression led to significantly reduced cell migration and tumor formation. To understand the mechanism of miR-497 tumor suppression, we identified clinically relevant target genes using a combination of RNA-sequencing data in an AS cell line, expression data from AS patients, and target prediction algorithms. This work provides insight into the mechanisms of miR-497 and its target genes in AS pathogenesis.
2023-10-19 | GSE240260 | GEO
Project description:To explore functionally crucial tumor-suppressive (TS)-miRNAs in hepatocellular carcinoma (HCC), we performed integrative function- and expression-based screenings of TS-miRNAs in six HCC cell lines. The screenings identified seven miRNAs, which showed growth-suppressive activities through the overexpression of each miRNA and were endogenously downregulated in HCC cell lines. Further expression analyses using a large panel of HCC cell lines and primary tumors demonstrated four miRNAs, miR-101, -195, -378 and -497, as candidate TS-miRNAs frequently silenced in HCCs. Among them, two clustered miRNAs miR-195 and miR-497 showed significant growth-suppressive activity with induction of G1 arrest. Comprehensive exploration of their targets using Argonute2-immunoprecipitation-deep-sequencing (Ago2-IP-seq) and genome-wide expression profiling after their overexpression, successfully identified a set of cell-cycle regulators, including CCNE1, CDC25A, CCND3, CDK4, and BTRC. Our results suggest the molecular pathway regulating cell cycle progression to be integrally altered by downregulation of miR-195 and miR-497 expression, leading to aberrant cell proliferation in hepatocarcinogenesis. Identification of miR-195 and miR-497 target genes by sequencing Ago2-binding mRNAs and total mRNAs of miR-195 or miR-497 overexpressed, or non-treated Hep G2 cell. Deep sequencing of RNAs in Ago2-IP fraction and mRNAs extracted from miR-195 or miR-497 overexpressed, or non-treated Hep G2 cell.
2013-05-31 | E-GEOD-41074 | biostudies-arrayexpress
Project description:To explore functionally crucial tumor-suppressive (TS)-miRNAs in hepatocellular carcinoma (HCC), we performed integrative function- and expression-based screenings of TS-miRNAs in six HCC cell lines. The screenings identified seven miRNAs, which showed growth-suppressive activities through the overexpression of each miRNA and were endogenously downregulated in HCC cell lines. Further expression analyses using a large panel of HCC cell lines and primary tumors demonstrated four miRNAs, miR-101, -195, -378 and -497, as candidate TS-miRNAs frequently silenced in HCCs. Among them, two clustered miRNAs miR-195 and miR-497 showed significant growth-suppressive activity with induction of G1 arrest. Comprehensive exploration of their targets using Argonute2-immunoprecipitation-deep-sequencing (Ago2-IP-seq) and genome-wide expression profiling after their overexpression, successfully identified a set of cell-cycle regulators, including CCNE1, CDC25A, CCND3, CDK4, and BTRC. Our results suggest the molecular pathway regulating cell cycle progression to be integrally altered by downregulation of miR-195 and miR-497 expression, leading to aberrant cell proliferation in hepatocarcinogenesis. Analysis of miRNA profile change in the Ago2-IP fraction after overexpression with miR-195 or miR-497 miRNA expression analysis using Immunopreticipated RNA fractions with anti-human-Argonute 2 antibody for non-treated, miR-195 or miR-497 overexpressed Hep G2 cell.
2013-05-31 | E-GEOD-41079 | biostudies-arrayexpress
Project description:To explore functionally crucial tumor-suppressive (TS)-miRNAs in hepatocellular carcinoma (HCC), we performed integrative function- and expression-based screenings of TS-miRNAs in six HCC cell lines. The screenings identified seven miRNAs, which showed growth-suppressive activities through the overexpression of each miRNA and were endogenously downregulated in HCC cell lines. Further expression analyses using a large panel of HCC cell lines and primary tumors demonstrated four miRNAs, miR-101, -195, -378 and -497, as candidate TS-miRNAs frequently silenced in HCCs. Among them, two clustered miRNAs miR-195 and miR-497 showed significant growth-suppressive activity with induction of G1 arrest. Comprehensive exploration of their targets using Argonute2-immunoprecipitation-deep-sequencing (Ago2-IP-seq) and genome-wide expression profiling after their overexpression, successfully identified a set of cell-cycle regulators, including CCNE1, CDC25A, CCND3, CDK4, and BTRC. Our results suggest the molecular pathway regulating cell cycle progression to be integrally altered by downregulation of miR-195 and miR-497 expression, leading to aberrant cell proliferation in hepatocarcinogenesis. Identification of miR-195 and miR-497 target genes by sequencing Ago2-binding mRNAs and total mRNAs of miR-195 or miR-497 overexpressed, or non-treated Hep G2 cell.
2013-05-31 | GSE41074 | GEO
Project description:To explore functionally crucial tumor-suppressive (TS)-miRNAs in hepatocellular carcinoma (HCC), we performed integrative function- and expression-based screenings of TS-miRNAs in six HCC cell lines. The screenings identified seven miRNAs, which showed growth-suppressive activities through the overexpression of each miRNA and were endogenously downregulated in HCC cell lines. Further expression analyses using a large panel of HCC cell lines and primary tumors demonstrated four miRNAs, miR-101, -195, -378 and -497, as candidate TS-miRNAs frequently silenced in HCCs. Among them, two clustered miRNAs miR-195 and miR-497 showed significant growth-suppressive activity with induction of G1 arrest. Comprehensive exploration of their targets using Argonute2-immunoprecipitation-deep-sequencing (Ago2-IP-seq) and genome-wide expression profiling after their overexpression, successfully identified a set of cell-cycle regulators, including CCNE1, CDC25A, CCND3, CDK4, and BTRC. Our results suggest the molecular pathway regulating cell cycle progression to be integrally altered by downregulation of miR-195 and miR-497 expression, leading to aberrant cell proliferation in hepatocarcinogenesis. Analysis of miRNA profile change in the Ago2-IP fraction after overexpression with miR-195 or miR-497
2013-05-31 | GSE41079 | GEO
Project description:Sulfur mustard (SM) is a hazardous chemical warfare agent. Exposure to SM results in various pathologies including skin lesions and impaired wound healing. To date, there are no effective treatments available. Here we discover that the miRNA miR-497-5p is induced in epidermal cells by SM and mediates keratinocyte dysfunction. Transcriptome analysis using RNA-seq in normal human epidermal keratinocytes (NHEK) revealed that SM evoked differential expression of 1,896 mRNAs and 25 miRNAs with many of these RNAs known to be involved in keratinocyte function and wound healing. We demonstrated that keratinocyte differentiation and proliferation were efficiently regulated by miRNAs induced in skin cells after exposure to SM. The inhibition of miR-497-5p counteracted SM-induced premature differentiation and inhibition of proliferation in NHEK. In addition, we showed that microneedle-mediated transdermal application of lipid-nanoparticles containing miR-497-5p inhibitor improved the healing of human skin biopsies upon exposure to SM. Our findings expand the current understanding of SM-associated molecular toxicology in keratinocytes and highlight miR-497-5p as feasible clinical target for specific skin therapy in SM-exposed patients and beyond.
2024-07-27 | GSE239682 | GEO
Project description:Objectives: Mounting evidence has demonstrated that microRNAs (miRNAs) participate in rheumatoid arthritis (RA). The role of highly conserved miR-15/107 family in RA was not clarified yet, and hence investigated in this study. Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to evaluate the expression of miRNAs and genes. Cell counting kit 8 (CCK-8) and FACS were used to detect proliferation and apoptosis. Protein expression was detected by using Western blotting. mRNA deep sequencing and cytokine antibody array were used to analyze differentially expressed genes, signaling pathways and cytokines. Results: In RA patients, the expression of miR-15a, miR-103, miR-497 and miR-646 was increased, while miR-424 was decreased. miR-424 and miR-497 were further investigated and the results showed that they could regulate multiple genes in rheumatoid arthritis synovial fibroblast (RASF) and affect signaling pathways. At the protein level, miR-497 mimic has an effect on all the selected inflammation related genes while miR-424 inhibitor only affects part of genes. miR-497 mimic has obvious effects on proliferation and apoptosis of RASF rather than miR-424 inhibitor. DICER1 was found to positively regulate miR-424 and miR-497, while DICER1 was also negatively regulated by miR-424. The increase of miR-424 could reduce miR-497 expression, thus forming a loop, which helps explain the dysregulated miR-424 and miR-497 condition in RA. Conclusion: Our study clarified the effects of miR-15/107 family members miR-424 and miR-497 on cell proliferation and apoptosis in RA and proposed miR-424-DICER1-miR-497 feedback loop which provided novel ideas and new inspiration for miRNA research and RA therapy.
2020-12-31 | GSE159618 | GEO
Project description:We found that miR-497 expression decrease in cSCC biopsies and cell lines compare to normal skin biopsies or normal keratinocytes cell. To understand in role lost expression of miR-497 might have in tumorigenesis of keratinocytes, we aimed to fine possible biochemical pathways and possible targets of miR-497 in cSCC. In order do so, we over expressed miR-497 in cSCC and used microarrays to fine global gene expression effected by miR-497.
2017-12-31 | GSE101096 | GEO
Project description:Patients with advanced colorectal cancer (CRC) are commonly treated with systemic combination therapy but suffer eventually from drug resistance. MicroRNAs (miRNAs) are suggested to play a role in treatment resistance of CRC. We studied whether restoring downregulated miR-195-5p and 497-5p sensitize CRC cells to currently used chemotherapeutics 5-fluorouracil, oxaliplatin and irinotecan. Sensitivity to 5-FU, oxaliplatin and irinotecan before and after transfection with miR-195-5p and miR-497-5p mimics was analyzed in CRC cell lines HCT116, RKO, DLD-1 and SW480. Mass spectrometry based proteomic analysis of transfected and wild-type cells was used to identify targets involved in sensitivity to chemotherapy. Proteomic analysis revealed 181 proteins with significantly altered expression after transfection with miR-195-5p mimic in HCT116 and RKO, including 118 downregulated and 63 upregulated proteins. After transfection with miR-497-5p mimic, 130 proteins were significantly downregulated and 102 were upregulated in HCT116 and RKO (P<0.05 and FC<-3 or FC>3). CHUK and LUZP1 were coinciding downregulated proteins in sensitized CRC cells after transfection with either mimic. Resistance mechanisms of these two proteins may be related to nuclear factor kappa-B signaling and G1 cell cycle arrest, respectively. Restoring miR-195-5p and miR-497-5p expression enhanced sensitivity to chemotherapy, mainly oxaliplatin, in CRC cells and could be a promising treatment strategy for patients with mCRC. Proteomics revealed potential targets of these miRNAs involved in sensitivity to chemotherapy.
2019-09-27 | PXD015369 | Pride
Project description:Despite considerable improvements in the treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), relapse is still associated with poor prognosis. We previously found that the risk for early relapse can be predicted by the rapid engraftment of patient-derived blasts transplanted into NOD/SCID mice. In search for the cellular and molecular profile associated with this phenotype, we investigated the expression of microRNAs (miRNAs) in different engraftment phenotypes and patient outcomes. We found miR-497~195 high expression in patient-derived xenograft samples with slow engraftment, derived from patients with favorable outcome. In contrast, epigenetic repression and low expression of these miRNAs was observed in rapidly engrafting samples, which were associated with early relapse. Overexpression of miR-497~195 in patient-derived cells suppressed in vivo engraftment of leukemia cells and considerably prolonged recipient survival by inhibition of regulators of cell cycle progression. As key factors for the entry in S phase were downregulated upon miR-497~195 overexpression, we identified CDK4/CCND3 mediated control of G1/S transition as a principal mechanism for miR-497~195 mediated suppression of leukemia progression in BCP-ALL. Thus, the association of the miR-497~195 cluster expression with outcome in BCP-ALL, and the importance of these miRNAs in counteracting the development of ALL in vivo indicate the relevance of the involved pathways as potential targets for therapeutic intervention.
2022-12-09 | GSE141774 | GEO