MicroRNAs regulate metabolic phenotypes during Multicellular Tumor Spheroids progression
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ABSTRACT:
PROVIDER: PRJEB41156 | ENA |
REPOSITORIES: ENA
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Project description:During tumor progression, cancer cells rewire their metabolism to face their bioenergetic demands. In recent years, microRNAs (miRNAs) have emerged as regulatory elements that inhibit the translation and stability of crucial mRNAs, some of them causing direct metabolic alterations in cancer. In this study, we investigated the relationship between miRNAs and their targets mRNAs that control metabolism, and how this fine-tuned regulation is diversified depending on the tumor stage. To do so, we implemented a paired analysis of RNA-seq and small RNA-seq in a breast cancer cell line (MCF7). The cell line was cultured in multicellular tumor spheroid (MCTS) and monoculture conditions. For MCTS, we selected two-time points during their development to recapitulate a proliferative and quiescent stage and contrast their miRNA and mRNA expression patterns associated with metabolism. As a result, we identified a set of new direct putative regulatory interactions between miRNAs and metabolic mRNAs representative for proliferative and quiescent stages. Notably, our study allows us to suggest that miR-3143 regulates the carbon metabolism by targeting hexokinase-2. Also, we found that the overexpression of several miRNAs could directly overturn the expression of mRNAs that control glycerophospholipid and N-Glycan metabolism. While this set of miRNAs downregulates their expression in the quiescent stage, the same set is upregulated in proliferative stages. This last finding suggests an additional metabolic switch of the above mentioned metabolic pathways between the quiescent and proliferative stages. Our results contribute to a better understanding of how miRNAs modulate the metabolic landscape in breast cancer MCTS, which eventually will help to design new strategies to mitigate cancer phenotype.
2020-11-11 | E-MTAB-9741 | biostudies-arrayexpress
Project description:During tumor progression, cancer cells rewire their metabolism to face their bioenergetic demands. In recent years, microRNAs (miRNAs) have emerged as regulatory elements that inhibit the translation and stability of crucial mRNAs, some of them causing direct metabolic alterations in cancer. In this study, we investigated the relationship between miRNAs and their targets mRNAs that control metabolism, and how this fine-tuned regulation is diversified depending on the tumor stage. To do so, we implemented a paired analysis of RNA-seq and small RNA-seq in a breast cancer cell line (MCF7). The cell line was cultured in multicellular tumor spheroid (MCTS) and monoculture conditions. For MCTS, we selected two-time points during their development to recapitulate a proliferative and quiescent stage and contrast their miRNA and mRNA expression patterns associated with metabolism. As a result, we identified a set of new direct putative regulatory interactions between miRNAs and metabolic mRNAs representative for proliferative and quiescent stages. Notably, our study allows us to suggest that miR-3143 regulates the carbon metabolism by targeting hexokinase-2. Also, we found that the overexpression of several miRNAs could directly overturn the expression of mRNAs that control glycerophospholipid and N-Glycan metabolism. While this set of miRNAs downregulates their expression in the quiescent stage, the same set is upregulated in proliferative stages. This last finding suggests an additional metabolic switch of the above mentioned metabolic pathways between the quiescent and proliferative stages. Our results contribute to a better understanding of how miRNAs modulate the metabolic landscape in breast cancer MCTS, which eventually will help to design new strategies to mitigate cancer phenotype.
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Project description:Human foreskin fibroblasts grown as multicellular spheroids or as a monolayer
2009-12-30 | E-MEXP-1226 | biostudies-arrayexpress
Project description:Microarray based mRNA profiling was used to charactarize the response to the compound VLX600 in cells grown as spheroids. Cells used was colon cancer cells HCT116 and HCT116HIF1a knock-out. We identify the small molecule VLX600 as a drug that is preferentially active against quiescent cells in colon cancer 3-D microtissues. The anticancer activity is associated with reduced mitochondrial respiration, leading to a bioenergetic catastrophe and tumor cell death. VLX600 shows enhanced cytotoxic activity under conditions of nutrient starvation. Microarray based mRNA profiling was used to charactarize the response to the compound VLX600 in cells grown as spheroids. Cells used was colon cancer cells HCT116 and HCT116HIF1a knock-out cells.
2014-02-17 | E-GEOD-53777 | biostudies-arrayexpress
Project description:Microarray based mRNA profiling was used to charactarize the response to the compound VLX600 in cells grown as spheroids. Cells used was colon cancer cells HCT116 and HCT116HIF1a knock-out.
2014-02-17 | GSE53777 | GEO
Project description:Multicellular Tumor Spheroids (MCTS) were pre-formed for 3 days with 786-O cell line to better mimic the tumor microenviroenment. These spheroids were treated with either vehicle (DMSO), drugs alone (KU-60019 10 μM; CX-4945 5 μM) or in combination (KU + CX) for 48h before RNA extraction.
2021-02-04 | E-MTAB-9977 | biostudies-arrayexpress
Project description:microRNAs in ovarian cancer cell spheroids
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Project description:To interrogate the hypoxia response pathways affected by the depletion of CAIX in BC cells, we performed gene expression profiling using SurePrint G3 Human Gene Expression 60K microarrays in MDA-MB-231-shCAIX, MCF7-shCAIX and the respective control cells grown as multicellular spheroids under hypoxic or normoxic conditions. The human breast cancer cell lines MDA-MB-231 and MCF7 were purchased from the European Collection of Cell Cultures (ECACC, UK) and maintained as recommended by the manufacturer. To generate stable CAIX silenced cells, cell lines were transfected with a pool of three plasmids each encoding CAIX-specific shRNA (1 µg) and a negative control (NC) plasmids encoding scrambled shRNAs (1 µg) (Santa Cruz Biotechnology, TX, USA) using shRNA transfection medium and shRNA transfection reagent (Santa Cruz Biotechnology, USA) according to the manufacturers’ protocol. For selection of stably transfected cells, puromycin dihydrochloride (Santa Cruz Biotechnology, USA) was added to medium 48 h post-transfection (6 µg/ml for MCF7, 2 µg/ml for MDA-MB-231 cells). The transfected cells were plated at density 2e+3 cells per ml of serum-free DMEM/F12 medium supplemented with EGF (20ng/ml, R&D Systems, #236-EG-200), bFGF (10ng/ml, SantaCruz, #sc-4573), hydrocortisone (50 ng/ml, Sigma-Aldrich, #H0135-1MG) and 1B27 (Invitrogen, #17504001) and grown as multicellular spheroids for 5 days. To establish hypoxic conditions, the cells were cultured at 1% oxygen, 94% N2 and 5% CO2 at 37oC using humidified multi-gas incubator (Sanyo, Sanyo Electric Co.,Ltd.) for 48 hours. The normoxic control cells were incubated at 37oC with 5% CO2 in a humidified incubator (Panasonic, Panasonic Healthcare Co., Ltd.). The efficiency of CAIX silencing was assessed by qRT-PCR and immunofluorescence before the experiments.
2018-01-01 | E-MTAB-5512 | biostudies-arrayexpress
Project description:Gene expression profiling of ovarian cancer spheroids upon treatment with three chemotherapy drugs
2008-05-06 | E-MEXP-1319 | biostudies-arrayexpress
Project description:Denunded HUVEC/HUASMC spheroids vs. HUASMC spheroids
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