Alteration of chromatin high‐order conformation associated with oxaliplatin resistance acquisition in colorectal cancer cells

Oxaliplatin is a first‐line chemotherapy drug widely adopted in colorectal cancer (CRC) treatment. However, a large proportion of patients tend to become resistant to oxaliplatin, causing chemotherapy to fail. At present, researches on oxaliplatin resistance mainly focus on the genetic and epigeneti...

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Published inExploration (Beijing, China) Vol. 3; no. 4; pp. 20220136 - n/a
Main Authors Li, Peilong, Shang, Xueying, Jiao, Qinlian, Mi, Qi, Zhu, Mengqian, Ren, Yidan, Li, Juan, Li, Li, Liu, Jin, Wang, Chuanxin, Shi, Yi, Wang, Yunshan, Du, Lutao
Format Journal Article
LanguageEnglish
Published China John Wiley & Sons, Inc 01.08.2023
Wiley
Subjects
3D spatial structure
Cancer
Cancer therapies
Chemotherapy
Chromatin
Chromosomes
Colorectal cancer
Colorectal carcinoma
Compartments
Conformation
Drug resistance
Epigenetics
Gene expression
Genetic transformation
Genomes
Genomic analysis
Metabolism
Metastases
multi‐omics
Oxaliplatin
oxaliplatin resistance
Reactive oxygen species
Tumor cells
Tumors
3D spatial structure
colorectal cancer
multi‐omics
oxaliplatin resistance
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Abstract Oxaliplatin is a first‐line chemotherapy drug widely adopted in colorectal cancer (CRC) treatment. However, a large proportion of patients tend to become resistant to oxaliplatin, causing chemotherapy to fail. At present, researches on oxaliplatin resistance mainly focus on the genetic and epigenetic alterations during cancer evolution, while the characteristics of high‐order three‐dimensional (3D) conformation of genome are yet to be explored. In order to investigate the chromatin conformation alteration during oxaliplatin resistance, we performed multi‐omics study by combining DLO Hi‐C, ChIP‐seq as well as RNA‐seq technologies on the established oxaliplatin‐resistant cell line HCT116‐OxR, as well as the control cell line HCT116. The results indicate that 19.33% of the genome regions have A/B compartments transformation after drug resistance, further analysis of the genes converted by A/B compartments reveals that the acquisition of oxaliplatin resistance in tumor cells is related to the reduction of reactive oxygen species and enhanced metastatic capacity. Our research reveals the spatial chromatin structural difference between CRC cells and oxaliplatin resistant cells based on the DLO Hi‐C and other epigenetic omics experiments. More importantly, we provide potential targets for oxaliplatin‐resistant cancer treatment and a new way to investigate drug resistance behavior under the perspective of 3D genome alteration. Our research reveals the spatial chromatin structural difference between colorectal cancer (CRC) cells and oxaliplatin resistant cells based on the DLO Hi‐C and other epigenetic omics experiments. More importantly, we provide a series of A/B compartment switching genes as potential targets for oxaliplatin‐resistant cancer treatment and find a new way to investigate drug resistance behavior under the perspective of 3D genome alteration.
AbstractList Oxaliplatin is a first‐line chemotherapy drug widely adopted in colorectal cancer (CRC) treatment. However, a large proportion of patients tend to become resistant to oxaliplatin, causing chemotherapy to fail. At present, researches on oxaliplatin resistance mainly focus on the genetic and epigenetic alterations during cancer evolution, while the characteristics of high‐order three‐dimensional (3D) conformation of genome are yet to be explored. In order to investigate the chromatin conformation alteration during oxaliplatin resistance, we performed multi‐omics study by combining DLO Hi‐C, ChIP‐seq as well as RNA‐seq technologies on the established oxaliplatin‐resistant cell line HCT116‐OxR, as well as the control cell line HCT116. The results indicate that 19.33% of the genome regions have A/B compartments transformation after drug resistance, further analysis of the genes converted by A/B compartments reveals that the acquisition of oxaliplatin resistance in tumor cells is related to the reduction of reactive oxygen species and enhanced metastatic capacity. Our research reveals the spatial chromatin structural difference between CRC cells and oxaliplatin resistant cells based on the DLO Hi‐C and other epigenetic omics experiments. More importantly, we provide potential targets for oxaliplatin‐resistant cancer treatment and a new way to investigate drug resistance behavior under the perspective of 3D genome alteration.
Abstract Oxaliplatin is a first‐line chemotherapy drug widely adopted in colorectal cancer (CRC) treatment. However, a large proportion of patients tend to become resistant to oxaliplatin, causing chemotherapy to fail. At present, researches on oxaliplatin resistance mainly focus on the genetic and epigenetic alterations during cancer evolution, while the characteristics of high‐order three‐dimensional (3D) conformation of genome are yet to be explored. In order to investigate the chromatin conformation alteration during oxaliplatin resistance, we performed multi‐omics study by combining DLO Hi‐C, ChIP‐seq as well as RNA‐seq technologies on the established oxaliplatin‐resistant cell line HCT116‐OxR, as well as the control cell line HCT116. The results indicate that 19.33% of the genome regions have A/B compartments transformation after drug resistance, further analysis of the genes converted by A/B compartments reveals that the acquisition of oxaliplatin resistance in tumor cells is related to the reduction of reactive oxygen species and enhanced metastatic capacity. Our research reveals the spatial chromatin structural difference between CRC cells and oxaliplatin resistant cells based on the DLO Hi‐C and other epigenetic omics experiments. More importantly, we provide potential targets for oxaliplatin‐resistant cancer treatment and a new way to investigate drug resistance behavior under the perspective of 3D genome alteration.
Oxaliplatin is a first‐line chemotherapy drug widely adopted in colorectal cancer (CRC) treatment. However, a large proportion of patients tend to become resistant to oxaliplatin, causing chemotherapy to fail. At present, researches on oxaliplatin resistance mainly focus on the genetic and epigenetic alterations during cancer evolution, while the characteristics of high‐order three‐dimensional (3D) conformation of genome are yet to be explored. In order to investigate the chromatin conformation alteration during oxaliplatin resistance, we performed multi‐omics study by combining DLO Hi‐C, ChIP‐seq as well as RNA‐seq technologies on the established oxaliplatin‐resistant cell line HCT116‐OxR, as well as the control cell line HCT116. The results indicate that 19.33% of the genome regions have A/B compartments transformation after drug resistance, further analysis of the genes converted by A/B compartments reveals that the acquisition of oxaliplatin resistance in tumor cells is related to the reduction of reactive oxygen species and enhanced metastatic capacity. Our research reveals the spatial chromatin structural difference between CRC cells and oxaliplatin resistant cells based on the DLO Hi‐C and other epigenetic omics experiments. More importantly, we provide potential targets for oxaliplatin‐resistant cancer treatment and a new way to investigate drug resistance behavior under the perspective of 3D genome alteration. Our research reveals the spatial chromatin structural difference between colorectal cancer (CRC) cells and oxaliplatin resistant cells based on the DLO Hi‐C and other epigenetic omics experiments. More importantly, we provide a series of A/B compartment switching genes as potential targets for oxaliplatin‐resistant cancer treatment and find a new way to investigate drug resistance behavior under the perspective of 3D genome alteration.
Oxaliplatin is a first-line chemotherapy drug widely adopted in colorectal cancer (CRC) treatment. However, a large proportion of patients tend to become resistant to oxaliplatin, causing chemotherapy to fail. At present, researches on oxaliplatin resistance mainly focus on the genetic and epigenetic alterations during cancer evolution, while the characteristics of high-order three-dimensional (3D) conformation of genome are yet to be explored. In order to investigate the chromatin conformation alteration during oxaliplatin resistance, we performed multi-omics study by combining DLO Hi-C, ChIP-seq as well as RNA-seq technologies on the established oxaliplatin-resistant cell line HCT116-OxR, as well as the control cell line HCT116. The results indicate that 19.33% of the genome regions have A/B compartments transformation after drug resistance, further analysis of the genes converted by A/B compartments reveals that the acquisition of oxaliplatin resistance in tumor cells is related to the reduction of reactive oxygen species and enhanced metastatic capacity. Our research reveals the spatial chromatin structural difference between CRC cells and oxaliplatin resistant cells based on the DLO Hi-C and other epigenetic omics experiments. More importantly, we provide potential targets for oxaliplatin-resistant cancer treatment and a new way to investigate drug resistance behavior under the perspective of 3D genome alteration.Oxaliplatin is a first-line chemotherapy drug widely adopted in colorectal cancer (CRC) treatment. However, a large proportion of patients tend to become resistant to oxaliplatin, causing chemotherapy to fail. At present, researches on oxaliplatin resistance mainly focus on the genetic and epigenetic alterations during cancer evolution, while the characteristics of high-order three-dimensional (3D) conformation of genome are yet to be explored. In order to investigate the chromatin conformation alteration during oxaliplatin resistance, we performed multi-omics study by combining DLO Hi-C, ChIP-seq as well as RNA-seq technologies on the established oxaliplatin-resistant cell line HCT116-OxR, as well as the control cell line HCT116. The results indicate that 19.33% of the genome regions have A/B compartments transformation after drug resistance, further analysis of the genes converted by A/B compartments reveals that the acquisition of oxaliplatin resistance in tumor cells is related to the reduction of reactive oxygen species and enhanced metastatic capacity. Our research reveals the spatial chromatin structural difference between CRC cells and oxaliplatin resistant cells based on the DLO Hi-C and other epigenetic omics experiments. More importantly, we provide potential targets for oxaliplatin-resistant cancer treatment and a new way to investigate drug resistance behavior under the perspective of 3D genome alteration.
Author Shi, Yi
Zhu, Mengqian
Li, Li
Wang, Chuanxin
Shang, Xueying
Mi, Qi
Liu, Jin
Li, Juan
Li, Peilong
Jiao, Qinlian
Ren, Yidan
Wang, Yunshan
Du, Lutao
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Issue 4
Keywords 3D spatial structure
colorectal cancer
multi‐omics
oxaliplatin resistance
Language English
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Notes Peilong Li, Xueying Shang, Qinlian Jiao, and Qi Mi contributed equally to this work.
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Snippet Oxaliplatin is a first‐line chemotherapy drug widely adopted in colorectal cancer (CRC) treatment. However, a large proportion of patients tend to become...
Oxaliplatin is a first-line chemotherapy drug widely adopted in colorectal cancer (CRC) treatment. However, a large proportion of patients tend to become...
Abstract Oxaliplatin is a first‐line chemotherapy drug widely adopted in colorectal cancer (CRC) treatment. However, a large proportion of patients tend to...
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StartPage 20220136
SubjectTerms 3D spatial structure
Cancer
Cancer therapies
Chemotherapy
Chromatin
Chromosomes
Colorectal cancer
Colorectal carcinoma
Compartments
Conformation
Drug resistance
Epigenetics
Gene expression
Genetic transformation
Genomes
Genomic analysis
Metabolism
Metastases
multi‐omics
Oxaliplatin
oxaliplatin resistance
Reactive oxygen species
Tumor cells
Tumors
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Title Alteration of chromatin high‐order conformation associated with oxaliplatin resistance acquisition in colorectal cancer cells
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