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RNA-sequencing dissects the transcriptome of polyploid cancer cells that resistant to combined treatments of cisplatin with paclitaxel and docetaxel

Abstract

Overcome chemoresistance will prevent cancer relapse and contribute to clinical chemotherapy. In order to explore the underlying mechanism of chemoresistance, we firstly incubated cancer cell with a combination of cisplatin+paclitaxel (C+P) or cisplatin+paclitaxel+docetaxel (C+P+D) to laboratorial mimic the treatment of cancer therapy. We found that polyploidy is a recurring strategy that cells adapt in response to cisplatin based treatments. Then RNA-sequencing was performed to identify differential expression genes (DEGs) that may contribute to drug resistance. DEGs with a number of 4830 and 5518 were discovered in C+P or C+P+D resistant cells respectively and 4384 (73.40%) genes were shared. Possible drug resistance genes like Atg14, Abcb1b, Tbx2, Slc2a9, Slc10a3, Slc22a18 were up regulated while Foxm1, Bcl2, Brca1, Chek1, Hiatl1 and Abcb9 were down regulated. Genes involved in pathways of p53 signaling, lysosome, apoptosis were up regulated, and in contrast, genes in cell cycle, DNA replication, and mismatch repair were down regulated. Moreover, representative proteins relative to DEGs were examined to validate the results of RNA-seq and RT-PCR. Taken together, these results will contribute to reveal the mechanism of chemoresistance and discover the potential prognostic factors for cancer medication.

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Supplementary files

Publication details

The article was received on 04 Jun 2017, accepted on 08 Aug 2017 and first published on 08 Aug 2017


Article type: Paper
DOI: 10.1039/C7MB00334J
Citation: Mol. BioSyst., 2017, Accepted Manuscript
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    RNA-sequencing dissects the transcriptome of polyploid cancer cells that resistant to combined treatments of cisplatin with paclitaxel and docetaxel

    Q. Wang, F. Lu and R. Lan, Mol. BioSyst., 2017, Accepted Manuscript , DOI: 10.1039/C7MB00334J

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