Suppressor microRNA-145 Is epigenetically regulated by promoter hypermethylation in esophageal squamous cell carcinoma

Kazuto Harada, Yoshifumi Baba, Takatsugu Ishimoto, Keisuke Kosumi, Ryuma Tokunaga, Daisuke Izumi, Mayuko Ohuchi, Kenichi Nakamura, Yuki Kiyozumi, Junji Kurashige, Shiro Iwagami, Yuji Miyamoto, Yasuo Sakamoto, Naoya Yoshida, Eiji Oki, Masayuki Watanabe, Hideo Baba

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background/Aim: DNA methylation is a common epigenetic change in cancer. However, microRNA (miRNA) regulation by epigenetic alteration, especially CpG island hypermethylation, remains poorly understood in esophageal squamous cell carcinoma (ESCC). Materials and Methods: miRNAs which were up-regulated after de-methylation with 5- aza-2'-deoxycytidine (5-AZA) were analyzed using the Human miFinder 384HC miScript miRNA PCR Array. The DNA methylation level was evaluated by bisulfite-pyrosequencing assay. Results: In two of the cell lines, 20 miRNAs, including miR-145-5p, were found to be up-regulated by more than three-fold after 5-AZA treatment. The miRNA-145 promoter was significantly more hypermethylated in the cancer tissues than in matched normal adjacent esophageal epithelial mucosa (p=0.0042; paired t-test). Moreover, the miRNA-145- 5p expression levels were significantly lower in cancerous tissues (p=0.0024). Conclusion: miRNA-145 expression in ESCC seems to be regulated by hypermethylation of the miRNA-145 promoter region.

Original languageEnglish
Pages (from-to)4617-4624
Number of pages8
JournalAnticancer research
Volume35
Issue number9
Publication statusPublished - Sep 1 2015

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MicroRNAs
decitabine
DNA Methylation
Epigenomics
CpG Islands
Esophageal Squamous Cell Carcinoma
Genetic Promoter Regions
Methylation
Neoplasms
Cell Line
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Harada, K., Baba, Y., Ishimoto, T., Kosumi, K., Tokunaga, R., Izumi, D., ... Baba, H. (2015). Suppressor microRNA-145 Is epigenetically regulated by promoter hypermethylation in esophageal squamous cell carcinoma. Anticancer research, 35(9), 4617-4624.

Suppressor microRNA-145 Is epigenetically regulated by promoter hypermethylation in esophageal squamous cell carcinoma. / Harada, Kazuto; Baba, Yoshifumi; Ishimoto, Takatsugu; Kosumi, Keisuke; Tokunaga, Ryuma; Izumi, Daisuke; Ohuchi, Mayuko; Nakamura, Kenichi; Kiyozumi, Yuki; Kurashige, Junji; Iwagami, Shiro; Miyamoto, Yuji; Sakamoto, Yasuo; Yoshida, Naoya; Oki, Eiji; Watanabe, Masayuki; Baba, Hideo.

In: Anticancer research, Vol. 35, No. 9, 01.09.2015, p. 4617-4624.

Research output: Contribution to journalArticle

Harada, K, Baba, Y, Ishimoto, T, Kosumi, K, Tokunaga, R, Izumi, D, Ohuchi, M, Nakamura, K, Kiyozumi, Y, Kurashige, J, Iwagami, S, Miyamoto, Y, Sakamoto, Y, Yoshida, N, Oki, E, Watanabe, M & Baba, H 2015, 'Suppressor microRNA-145 Is epigenetically regulated by promoter hypermethylation in esophageal squamous cell carcinoma', Anticancer research, vol. 35, no. 9, pp. 4617-4624.
Harada K, Baba Y, Ishimoto T, Kosumi K, Tokunaga R, Izumi D et al. Suppressor microRNA-145 Is epigenetically regulated by promoter hypermethylation in esophageal squamous cell carcinoma. Anticancer research. 2015 Sep 1;35(9):4617-4624.
Harada, Kazuto ; Baba, Yoshifumi ; Ishimoto, Takatsugu ; Kosumi, Keisuke ; Tokunaga, Ryuma ; Izumi, Daisuke ; Ohuchi, Mayuko ; Nakamura, Kenichi ; Kiyozumi, Yuki ; Kurashige, Junji ; Iwagami, Shiro ; Miyamoto, Yuji ; Sakamoto, Yasuo ; Yoshida, Naoya ; Oki, Eiji ; Watanabe, Masayuki ; Baba, Hideo. / Suppressor microRNA-145 Is epigenetically regulated by promoter hypermethylation in esophageal squamous cell carcinoma. In: Anticancer research. 2015 ; Vol. 35, No. 9. pp. 4617-4624.
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abstract = "Background/Aim: DNA methylation is a common epigenetic change in cancer. However, microRNA (miRNA) regulation by epigenetic alteration, especially CpG island hypermethylation, remains poorly understood in esophageal squamous cell carcinoma (ESCC). Materials and Methods: miRNAs which were up-regulated after de-methylation with 5- aza-2'-deoxycytidine (5-AZA) were analyzed using the Human miFinder 384HC miScript miRNA PCR Array. The DNA methylation level was evaluated by bisulfite-pyrosequencing assay. Results: In two of the cell lines, 20 miRNAs, including miR-145-5p, were found to be up-regulated by more than three-fold after 5-AZA treatment. The miRNA-145 promoter was significantly more hypermethylated in the cancer tissues than in matched normal adjacent esophageal epithelial mucosa (p=0.0042; paired t-test). Moreover, the miRNA-145- 5p expression levels were significantly lower in cancerous tissues (p=0.0024). Conclusion: miRNA-145 expression in ESCC seems to be regulated by hypermethylation of the miRNA-145 promoter region.",
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AU - Harada, Kazuto

AU - Baba, Yoshifumi

AU - Ishimoto, Takatsugu

AU - Kosumi, Keisuke

AU - Tokunaga, Ryuma

AU - Izumi, Daisuke

AU - Ohuchi, Mayuko

AU - Nakamura, Kenichi

AU - Kiyozumi, Yuki

AU - Kurashige, Junji

AU - Iwagami, Shiro

AU - Miyamoto, Yuji

AU - Sakamoto, Yasuo

AU - Yoshida, Naoya

AU - Oki, Eiji

AU - Watanabe, Masayuki

AU - Baba, Hideo

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N2 - Background/Aim: DNA methylation is a common epigenetic change in cancer. However, microRNA (miRNA) regulation by epigenetic alteration, especially CpG island hypermethylation, remains poorly understood in esophageal squamous cell carcinoma (ESCC). Materials and Methods: miRNAs which were up-regulated after de-methylation with 5- aza-2'-deoxycytidine (5-AZA) were analyzed using the Human miFinder 384HC miScript miRNA PCR Array. The DNA methylation level was evaluated by bisulfite-pyrosequencing assay. Results: In two of the cell lines, 20 miRNAs, including miR-145-5p, were found to be up-regulated by more than three-fold after 5-AZA treatment. The miRNA-145 promoter was significantly more hypermethylated in the cancer tissues than in matched normal adjacent esophageal epithelial mucosa (p=0.0042; paired t-test). Moreover, the miRNA-145- 5p expression levels were significantly lower in cancerous tissues (p=0.0024). Conclusion: miRNA-145 expression in ESCC seems to be regulated by hypermethylation of the miRNA-145 promoter region.

AB - Background/Aim: DNA methylation is a common epigenetic change in cancer. However, microRNA (miRNA) regulation by epigenetic alteration, especially CpG island hypermethylation, remains poorly understood in esophageal squamous cell carcinoma (ESCC). Materials and Methods: miRNAs which were up-regulated after de-methylation with 5- aza-2'-deoxycytidine (5-AZA) were analyzed using the Human miFinder 384HC miScript miRNA PCR Array. The DNA methylation level was evaluated by bisulfite-pyrosequencing assay. Results: In two of the cell lines, 20 miRNAs, including miR-145-5p, were found to be up-regulated by more than three-fold after 5-AZA treatment. The miRNA-145 promoter was significantly more hypermethylated in the cancer tissues than in matched normal adjacent esophageal epithelial mucosa (p=0.0042; paired t-test). Moreover, the miRNA-145- 5p expression levels were significantly lower in cancerous tissues (p=0.0024). Conclusion: miRNA-145 expression in ESCC seems to be regulated by hypermethylation of the miRNA-145 promoter region.

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