Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Cis-platin resistant cell lines and sensitive parental cell lines: microRNA profiling by array

ABSTRACT: This miRNA microarray experiment is part of the same multi-omics study as the RNA-seq and whole-exome sequencing data deposited in the European Nucleotide Archive under accession PRJEB122863. The aim of this study was to identify prognostic molecular signatures for GTC patients derived from comprehensive molecular characterization of cisplatin-resistant variants of established GCT cell lines. GCT cell lines and their isogenic cisplatin-resistant variants (2102Ep, NCCIT, NT2, JAR, JEG3, NOY1, NCR-G1, and TCam2) were profiled by RNA-, microRNA-, and whole-exome sequencing (WES).

ORGANISM(S): Homo sapiens

SUBMITTER: Dominik Hadzega

PROVIDER: E-MTAB-17459 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Understanding the mechanism of resistance in platinum-based regimens for the treatment of high-grade serous ovarian cancer (HGSOC) is important for identifying new therapeutic targets to improve the clinical outcome of ovarian cancer patients. Mass spectrometry-based proteomic strategy was applied to spheroidal cisplatin sensitive and resistant HGSOC generated cell lines in the absence and presence of cisplatin drug. A complete expressed HGSOC proteome and phosphoproteome was characterized in cisplatin sensitive and resistant HGSOC cell lines providing insight into the mechanism of resistance development. PCA analysis showed that phosphorylation of a few proteins provides better classification than the whole proteome of the cellular subtypes. Specifically, a distinctive phosphoproteomic signature between cisplatin sensitive and resistant cell lines in the absence of drug was observed. This same phosphoproteomic signature was observed in our cisplatin sensitive cell line in the absence and presence of drug, indicating a vital role for phosphorylation of proteins in resistance development to cisplatin. The most phosphorylated protein was sequestosome (p62/SQSTM1). Differential expressions of apoptosis by the prognostic factor ratio of Bcl-2/Bax and autophagy, known to be regulated by p62/SQSTM1, was validated in the proteome data and by western blot analysis. A significant increase in apoptosis in the presence of cisplatin was observed in only the sensitive cell line while autophagy revealed increased expression in the resistant relative to sensitive cell line. Furthermore, site specific phosphorylation on 20 modified residues of sequestosome was characterized. Elevated expression of phosphorylation of sequestosome in resistant HGSOC cell lines was validated with western blot analysis. Here, we propose phosphorylation of sequestosome to be a marker and key in cisplatin resistance development in HGOSC ovarian cancers by shuttling ubiquitinated proteins to the autophagy pathway and influencing down-regulation of apoptosis.

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Cis-platin resistant cell lines and sensitive parental cell lines: microRNA profiling by array

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