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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

Molecular interactions of genes.The interactions were analyzed by Cytoscape_3.2.0 plugin GeneMANIAThe query genes were marked blue, and the genes in 17-gene signature were marked yellow.
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f4: Molecular interactions of genes.The interactions were analyzed by Cytoscape_3.2.0 plugin GeneMANIAThe query genes were marked blue, and the genes in 17-gene signature were marked yellow.

Mentions: In order to better understand the molecular interaction of these genes, the interaction network of the genes were analyzed by Cytoscape 3.2.019 plugin GeneMANIA20, where gene interactions were collected from interaction datasets BioGRID21. In such analysis, two genes are functionally linked if the effects of perturbing one gene were found to be modified by perturbations to a second gene. As data showed (Fig. 4), these genes showed extensive co-expression, genetic interactions and physical interactions, suggesting they are densely connected to modulate chemoresistance development. Among them, EMT regulators, such as CDH1, EPCAM, CDH256 were in the central place of the network, suggesting again the importance of EMT pathway. Furthermore, several genes such as CAPN2, TUSC3 and CYBRD1, played as central factors in the networks and validated in clinical samples as we demonstrated later. Therefore, their molecular mechanisms are worth exploring.


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)

Molecular interactions of genes.The interactions were analyzed by Cytoscape_3.2.0 plugin GeneMANIAThe query genes were marked blue, and the genes in 17-gene signature were marked yellow.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Molecular interactions of genes.The interactions were analyzed by Cytoscape_3.2.0 plugin GeneMANIAThe query genes were marked blue, and the genes in 17-gene signature were marked yellow.
Mentions: In order to better understand the molecular interaction of these genes, the interaction network of the genes were analyzed by Cytoscape 3.2.019 plugin GeneMANIA20, where gene interactions were collected from interaction datasets BioGRID21. In such analysis, two genes are functionally linked if the effects of perturbing one gene were found to be modified by perturbations to a second gene. As data showed (Fig. 4), these genes showed extensive co-expression, genetic interactions and physical interactions, suggesting they are densely connected to modulate chemoresistance development. Among them, EMT regulators, such as CDH1, EPCAM, CDH256 were in the central place of the network, suggesting again the importance of EMT pathway. Furthermore, several genes such as CAPN2, TUSC3 and CYBRD1, played as central factors in the networks and validated in clinical samples as we demonstrated later. Therefore, their molecular mechanisms are worth exploring.

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