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Transcriptomic differences between radioresistant MDA-MB-468 and parental MDA-MB-468

ABSTRACT: Transcriptomic differences between radioresistant MDA-MB-468 and parental MDA-MB-468

PROVIDER: PRJNA1223424 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32334719_1.fastq.gz	Fastqsanger.gz
	SRR32334719_2.fastq.gz	Fastqsanger.gz
	SRR32334720_1.fastq.gz	Fastqsanger.gz
	SRR32334720_2.fastq.gz	Fastqsanger.gz
	SRR32334721_1.fastq.gz	Fastqsanger.gz

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Transcriptomic differences between radioresistant MDA-MB-468 and parental MDA-MB-468

Project description:A radioresistant MDA-MB-468 cell line, a human TNBC cell lines, was developed by giving a total dose of 50Gy (2gyx5, 4Gyx3, 6Gyx3, and 10Gyx1) to the parental cell line. The trancriptomic changes that occur include enhanced antioxidant response, increase in DNA repair pathways, and invasion/metastasis features.

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Project description:In this experiment, we generated isogenic carboplatin-resistant MDA-MB-468 cells displaying a 5x increase in IC50 in respect to the parental cell line. We set out to compare the transcriptome of these cell lines, together with MDA-MB-468 cells overexpressing a constitutively active form of beta-catenin to understand underlying transcriptional changes supporting stable carboplatin-tolerance.

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Project description:To provide preliminary insights into metabolic and lipidomic characteristics in radioresistant triple-negative breast cancer (TNBC) cells and suggest potential therapeutic targets, we performed a comprehensive metabolic and lipidomic profiling of radioresistant MDA-MB-231 (MDA-MB-231/RR) TNBC cells and their parental cells using gas chromatography-mass spectrometry and nano electrospray ionization-mass spectrometry, followed by multivariate statistical analysis. Buthionine sulfoximine (BSO) and radiation were co-treated to radioresistant TNBC cells. The level of glutathione (GSH) was significantly increased, and the levels of GSH synthesis-related metabolites, such as cysteine, glycine, and glutamine were also increased in MDA-MB-231/RR cells. In contrast, the level of lactic acid was significantly reduced. In addition, reactive oxygen species (ROS) level was decreased in MDA-MB-231/RR cells. In the lipidomic profiles of MDA-MB-231/RR cells, the levels of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were significantly increased, whereas those of most of the phosphatidylinositol species were significantly decreased. BSO sensitized MDA-MB-231/RR cells to radiotherapy, which resulted in decreased GSH level and increased ROS level and apoptosis. Radioresistant TNBC cells showed distinct metabolic and lipidomic characteristics compared to their parental cells. We suggested activated GSH, PC, and PE biosynthesis pathways as potential targets for treating radioresistant TNBC cells. Particularly, enhanced radiosensitivity was achieved by inhibition of GSH biosynthesis in MDA-MB-231/RR cells.

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