Transcriptomics,Genomics

Dataset Information

28

An epigenomic approach to identifying differential overlapping and cis-acting lncRNAs in cisplatin-resistant cancer cells


ABSTRACT: Long noncoding RNAs are newly discovered regulators that play a critical role in cell biology, crucial to the correct functioning of the cell. Alterations in lncRNAs can lead to the development of diseases such as cancer. However, the role of lncRNAs in resistance to platinum chemotherapy is largely unknown. To screen for epigenetic changes involved in the development of resistance, we combined lncRNA and mRNA expression microarrays with whole genome bisulfite sequencing (WGBS) in four paired cisplatin-sensitive/resistant cells from non-small cell lung cancer and ovarian cancer. We found low levels of expression changes in lncRNAs (1.5%) and mRNAs (2%) when comparing resistant vs. sensitive cells. The correlation between lncRNA/mRNA arrays and WGBS identified two groups of lncRNAs, classified according to their relationship with the gene they have in silico complementarity or with their possible epigenetic regulation at the DNA methylation level. Validation of the results of expression and methylation levels allowed us to characterize lncRNAs in cisplatin-resistant phenotypes. In this study, we characterized lncRNAs that change in cisplatin-resistant cells due to epigenetic regulation at the DNA methylation level and the associated changes in expression levels. We have identified two groups of differentially expressed and methylated lncRNAs, indicating a new approach to the study of the mechanisms involved in the development of acquired resistance to cisplatin in cancer cells. Overall design: A total of four cell lines were purchased from ATCC and ECACC (Sigma-Aldrich) and cultured as recommended. To analyze the changes in the transcriptome as a result of CDDP treatment, we established the CDDP-resistant variants of H23-R, H460-R, A2780-R and OVCAR3-R from the parental-sensitive variants H23, H460, A2780 and OVCAR3, after exposure to increasing doses of CDDP treatment in a time period of 6–18 months. Labelled cDNA from the 8 cell lines was hybridized by duplicate into the Human LncRNA Array v3.0 (8 x 60K, Arraystar).

INSTRUMENT(S): Agilent-045997 Arraystar human lncRNA microarray V3 (Probe Name Version)

SUBMITTER: Carlos Rodriguez Antolin 

PROVIDER: GSE108139 | GEO | 2018-06-14

REPOSITORIES: GEO

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Publications

An epigenomic approach to identifying differential overlapping and cis-acting lncRNAs in cisplatin-resistant cancer cells.

Vera Olga O   Rodriguez-Antolin Carlos C   de Castro Javier J   Karreth Florian A FA   Sellers Thomas A TA   Ibanez de Caceres Inmaculada I  

Epigenetics 20180402 3


Long noncoding RNAs (lncRNAs) are critical regulators of cell biology whose alteration can lead to the development of diseases such as cancer. The potential role of lncRNAs and their epigenetic regulation in response to platinum treatment are largely unknown. We analyzed four paired cisplatin-sensitive/resistant non-small cell lung cancer and ovarian cancer cell lines. The epigenetic landscape of overlapping and cis-acting lncRNAs was determined by combining human microarray data on 30,586 lncRN  ...[more]

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