ONCOmmunity

Suppressor microRNA-145 Is Epigenetically Regulated by Promoter Hypermethylation in Esophageal Squamous Cell Carcinoma.

By: 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

Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
2015-8-9; doi:

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

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.