Identification of novel hypermethylated genes and demethylating effect of vincristine in colorectal cancer

Ji Wook Moon, Soo Kyung Lee, Jung Ok Lee, Nami Kim, Yong Woo Lee, Su Jin Kim, Ho Jin Kang, Jin Kim, Hyeon Soo Kim, Sun-Hwa Park

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Colorectal cancer (CRC) arises as a consequence of genetic events such as gene mutation and epigenetic alteration. The aim of this study was to identify new hypermethylated candidate genes and methylation-based therapeutic targets using vincristine in CRC. Methods. We analyzed the methylation status of 27,578 CpG sites spanning more than 14,000 genes in CRC tissues compared with adjacent normal tissues and normal colon tissues using Illumina bead chip array. Twenty-one hypermethylated genes and 18 CpG island methylator phenotype markers were selected as candidate genes. The methylation status of 39 genes was validated by quantitative methylation-specific polymerase chain reaction in CRC tissues, adjacent normal tissues, normal colon cells, and three CRC cell lines. Of these, 29 hypermethylated candidate genes were investigated using the demethylating effects of 5-aza-2′-deoxycytidine (5-aza-dC) and vincristine in CRC cells. Results: Thirty-two out of 39 genes were hypermethylated in CRC tissues compared with adjacent normal tissues. Vincristine induced demethylation of methylated genes in CRC cells to the same extent as 5-aza-dC. The mRNA expression of AKR1B1, CHST10, ELOVL4, FLI1, SOX5, STK33, and ZNF304 was restored by treatment with 5-aza-dC and vincristine. Conclusion: These results suggest that these novel hypermethylated genes AKR1B1, CHST10, ELOVL4, SOX5, STK33, and ZNF304 may be potential methylation biomarkers and therapeutic targets of vincristine in CRC.

Original languageEnglish
Article number4
JournalJournal of Experimental and Clinical Cancer Research
Volume33
Issue number1
DOIs
Publication statusPublished - 2014 Jan 6

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Vincristine
Colorectal Neoplasms
decitabine
Methylation
Genes
Colon
CpG Islands
Epigenomics
Biomarkers
Phenotype
Cell Line
Polymerase Chain Reaction
Messenger RNA
Mutation

Keywords

  • 5-aza-2′-deoxycytidine
  • CIMP markers
  • Colorectal cancer
  • Hypermethylated genes
  • Therapeutic targets
  • Vincristine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Identification of novel hypermethylated genes and demethylating effect of vincristine in colorectal cancer. / Moon, Ji Wook; Lee, Soo Kyung; Lee, Jung Ok; Kim, Nami; Lee, Yong Woo; Kim, Su Jin; Kang, Ho Jin; Kim, Jin; Kim, Hyeon Soo; Park, Sun-Hwa.

In: Journal of Experimental and Clinical Cancer Research, Vol. 33, No. 1, 4, 06.01.2014.

Research output: Contribution to journalArticle

Moon, Ji Wook ; Lee, Soo Kyung ; Lee, Jung Ok ; Kim, Nami ; Lee, Yong Woo ; Kim, Su Jin ; Kang, Ho Jin ; Kim, Jin ; Kim, Hyeon Soo ; Park, Sun-Hwa. / Identification of novel hypermethylated genes and demethylating effect of vincristine in colorectal cancer. In: Journal of Experimental and Clinical Cancer Research. 2014 ; Vol. 33, No. 1.
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abstract = "Background: Colorectal cancer (CRC) arises as a consequence of genetic events such as gene mutation and epigenetic alteration. The aim of this study was to identify new hypermethylated candidate genes and methylation-based therapeutic targets using vincristine in CRC. Methods. We analyzed the methylation status of 27,578 CpG sites spanning more than 14,000 genes in CRC tissues compared with adjacent normal tissues and normal colon tissues using Illumina bead chip array. Twenty-one hypermethylated genes and 18 CpG island methylator phenotype markers were selected as candidate genes. The methylation status of 39 genes was validated by quantitative methylation-specific polymerase chain reaction in CRC tissues, adjacent normal tissues, normal colon cells, and three CRC cell lines. Of these, 29 hypermethylated candidate genes were investigated using the demethylating effects of 5-aza-2′-deoxycytidine (5-aza-dC) and vincristine in CRC cells. Results: Thirty-two out of 39 genes were hypermethylated in CRC tissues compared with adjacent normal tissues. Vincristine induced demethylation of methylated genes in CRC cells to the same extent as 5-aza-dC. The mRNA expression of AKR1B1, CHST10, ELOVL4, FLI1, SOX5, STK33, and ZNF304 was restored by treatment with 5-aza-dC and vincristine. Conclusion: These results suggest that these novel hypermethylated genes AKR1B1, CHST10, ELOVL4, SOX5, STK33, and ZNF304 may be potential methylation biomarkers and therapeutic targets of vincristine in CRC.",
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N2 - Background: Colorectal cancer (CRC) arises as a consequence of genetic events such as gene mutation and epigenetic alteration. The aim of this study was to identify new hypermethylated candidate genes and methylation-based therapeutic targets using vincristine in CRC. Methods. We analyzed the methylation status of 27,578 CpG sites spanning more than 14,000 genes in CRC tissues compared with adjacent normal tissues and normal colon tissues using Illumina bead chip array. Twenty-one hypermethylated genes and 18 CpG island methylator phenotype markers were selected as candidate genes. The methylation status of 39 genes was validated by quantitative methylation-specific polymerase chain reaction in CRC tissues, adjacent normal tissues, normal colon cells, and three CRC cell lines. Of these, 29 hypermethylated candidate genes were investigated using the demethylating effects of 5-aza-2′-deoxycytidine (5-aza-dC) and vincristine in CRC cells. Results: Thirty-two out of 39 genes were hypermethylated in CRC tissues compared with adjacent normal tissues. Vincristine induced demethylation of methylated genes in CRC cells to the same extent as 5-aza-dC. The mRNA expression of AKR1B1, CHST10, ELOVL4, FLI1, SOX5, STK33, and ZNF304 was restored by treatment with 5-aza-dC and vincristine. Conclusion: These results suggest that these novel hypermethylated genes AKR1B1, CHST10, ELOVL4, SOX5, STK33, and ZNF304 may be potential methylation biomarkers and therapeutic targets of vincristine in CRC.

AB - Background: Colorectal cancer (CRC) arises as a consequence of genetic events such as gene mutation and epigenetic alteration. The aim of this study was to identify new hypermethylated candidate genes and methylation-based therapeutic targets using vincristine in CRC. Methods. We analyzed the methylation status of 27,578 CpG sites spanning more than 14,000 genes in CRC tissues compared with adjacent normal tissues and normal colon tissues using Illumina bead chip array. Twenty-one hypermethylated genes and 18 CpG island methylator phenotype markers were selected as candidate genes. The methylation status of 39 genes was validated by quantitative methylation-specific polymerase chain reaction in CRC tissues, adjacent normal tissues, normal colon cells, and three CRC cell lines. Of these, 29 hypermethylated candidate genes were investigated using the demethylating effects of 5-aza-2′-deoxycytidine (5-aza-dC) and vincristine in CRC cells. Results: Thirty-two out of 39 genes were hypermethylated in CRC tissues compared with adjacent normal tissues. Vincristine induced demethylation of methylated genes in CRC cells to the same extent as 5-aza-dC. The mRNA expression of AKR1B1, CHST10, ELOVL4, FLI1, SOX5, STK33, and ZNF304 was restored by treatment with 5-aza-dC and vincristine. Conclusion: These results suggest that these novel hypermethylated genes AKR1B1, CHST10, ELOVL4, SOX5, STK33, and ZNF304 may be potential methylation biomarkers and therapeutic targets of vincristine in CRC.

KW - 5-aza-2′-deoxycytidine

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KW - Therapeutic targets

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