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Genome-wide profiles of methylation, microRNAs, and gene expression in chemoresistant breast cancer.

He DX, Gu F, Gao F, Hao JJ, Gong D, Gu XT, Mao AQ, Jin J, Fu L, Ma X - Sci Rep (2016)

Bottom Line: Cancer chemoresistance is regulated by complex genetic and epigenetic networks.In this study, the features of gene expression, methylation, and microRNA (miRNA) expression were investigated with high-throughput sequencing in human breast cancer MCF-7 cells resistant to adriamycin (MCF-7/ADM) and paclitaxel (MCF-7/PTX).In conclusion, our results have generated a new workflow for the integrated analysis of the effects of miRNAs and methylation on gene expression during the development of chemoresistance.

View Article: PubMed Central - PubMed

Affiliation: National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.

ABSTRACT
Cancer chemoresistance is regulated by complex genetic and epigenetic networks. In this study, the features of gene expression, methylation, and microRNA (miRNA) expression were investigated with high-throughput sequencing in human breast cancer MCF-7 cells resistant to adriamycin (MCF-7/ADM) and paclitaxel (MCF-7/PTX). We found that: ① both of the chemoresistant cell lines had similar, massive changes in gene expression, methylation, and miRNA expression versus chemosensitive controls. ② Pairwise integration of the data highlighted sets of genes that were regulated by either methylation or miRNAs, and sets of miRNAs whose expression was controlled by DNA methylation in chemoresistant cells. ③ By combining the three sets of high-throughput data, we obtained a list of genes whose expression was regulated by both methylation and miRNAs in chemoresistant cells; ④ Expression of these genes was then validated in clinical breast cancer samples to generate a 17-gene signature that showed good predictive and prognostic power in triple-negative breast cancer patients receiving anthracycline-taxane-based neoadjuvant chemotherapy. In conclusion, our results have generated a new workflow for the integrated analysis of the effects of miRNAs and methylation on gene expression during the development of chemoresistance.

No MeSH data available.


Related in: MedlinePlus

Generation of comparative profiles of DNA methylation, mRNA and miRNA expression.(a) Hierarchical clustering of the methylation status in MCF-7/ADM, /PTX, and /WT cells. (b) Venn diagrams of the DMRs of the three comparison groups. (c,d) Scatter-plots of the differentially-expressed mRNAs (c) and miRNAs (d). Fold-changes of mRNAs and miRNAs are shown on the X or Y axis as Log (fold-change value).
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f1: Generation of comparative profiles of DNA methylation, mRNA and miRNA expression.(a) Hierarchical clustering of the methylation status in MCF-7/ADM, /PTX, and /WT cells. (b) Venn diagrams of the DMRs of the three comparison groups. (c,d) Scatter-plots of the differentially-expressed mRNAs (c) and miRNAs (d). Fold-changes of mRNAs and miRNAs are shown on the X or Y axis as Log (fold-change value).

Mentions: Hierarchical clustering analysis of their methylation status showed that MCF-7/ADM and MCF-7/PTX cells fell into the same cluster, but were separate from the parental control MCF-7/WT cells (Fig. 1a). Pair-wise comparisons were performed among the three cell lines to identify the differentially-methylated regions (DMRs) with statistical significance (median β differences >0.20, p < 0.01), and DMRs were then annotated to genes based on their genomic positions. The majority of the DMRs were allocated to gene-body regions and intergenic regions, while <15% were in promoters and the 5′-UTR (Fig. S2c). Furthermore, most of the DMRs in genes overlapped in the two chemoresistant groups compared with their chemosensitive comparison groups (Fig. 1b). Therefore, these data suggested that the methylation pattern is similar in the two chemoresistant cell lines.


Genome-wide profiles of methylation, microRNAs, and gene expression in chemoresistant breast cancer.

He DX, Gu F, Gao F, Hao JJ, Gong D, Gu XT, Mao AQ, Jin J, Fu L, Ma X - Sci Rep (2016)

Generation of comparative profiles of DNA methylation, mRNA and miRNA expression.(a) Hierarchical clustering of the methylation status in MCF-7/ADM, /PTX, and /WT cells. (b) Venn diagrams of the DMRs of the three comparison groups. (c,d) Scatter-plots of the differentially-expressed mRNAs (c) and miRNAs (d). Fold-changes of mRNAs and miRNAs are shown on the X or Y axis as Log (fold-change value).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837395&req=5

f1: Generation of comparative profiles of DNA methylation, mRNA and miRNA expression.(a) Hierarchical clustering of the methylation status in MCF-7/ADM, /PTX, and /WT cells. (b) Venn diagrams of the DMRs of the three comparison groups. (c,d) Scatter-plots of the differentially-expressed mRNAs (c) and miRNAs (d). Fold-changes of mRNAs and miRNAs are shown on the X or Y axis as Log (fold-change value).
Mentions: Hierarchical clustering analysis of their methylation status showed that MCF-7/ADM and MCF-7/PTX cells fell into the same cluster, but were separate from the parental control MCF-7/WT cells (Fig. 1a). Pair-wise comparisons were performed among the three cell lines to identify the differentially-methylated regions (DMRs) with statistical significance (median β differences >0.20, p < 0.01), and DMRs were then annotated to genes based on their genomic positions. The majority of the DMRs were allocated to gene-body regions and intergenic regions, while <15% were in promoters and the 5′-UTR (Fig. S2c). Furthermore, most of the DMRs in genes overlapped in the two chemoresistant groups compared with their chemosensitive comparison groups (Fig. 1b). Therefore, these data suggested that the methylation pattern is similar in the two chemoresistant cell lines.

Bottom Line: Cancer chemoresistance is regulated by complex genetic and epigenetic networks.In this study, the features of gene expression, methylation, and microRNA (miRNA) expression were investigated with high-throughput sequencing in human breast cancer MCF-7 cells resistant to adriamycin (MCF-7/ADM) and paclitaxel (MCF-7/PTX).In conclusion, our results have generated a new workflow for the integrated analysis of the effects of miRNAs and methylation on gene expression during the development of chemoresistance.

View Article: PubMed Central - PubMed

Affiliation: National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.

ABSTRACT
Cancer chemoresistance is regulated by complex genetic and epigenetic networks. In this study, the features of gene expression, methylation, and microRNA (miRNA) expression were investigated with high-throughput sequencing in human breast cancer MCF-7 cells resistant to adriamycin (MCF-7/ADM) and paclitaxel (MCF-7/PTX). We found that: ① both of the chemoresistant cell lines had similar, massive changes in gene expression, methylation, and miRNA expression versus chemosensitive controls. ② Pairwise integration of the data highlighted sets of genes that were regulated by either methylation or miRNAs, and sets of miRNAs whose expression was controlled by DNA methylation in chemoresistant cells. ③ By combining the three sets of high-throughput data, we obtained a list of genes whose expression was regulated by both methylation and miRNAs in chemoresistant cells; ④ Expression of these genes was then validated in clinical breast cancer samples to generate a 17-gene signature that showed good predictive and prognostic power in triple-negative breast cancer patients receiving anthracycline-taxane-based neoadjuvant chemotherapy. In conclusion, our results have generated a new workflow for the integrated analysis of the effects of miRNAs and methylation on gene expression during the development of chemoresistance.

No MeSH data available.


Related in: MedlinePlus