Comprehensive analysis of the relationship between DNA methylation and miRNA expression in esophageal carcinoma

• Project/Area Number: 15K10104
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: SAITOU Seiya 熊本大学, 医学部附属病院, 非常勤診療医師 (00594475)
• Co-Investigator(Kenkyū-buntansha): 坂本 快郎 熊本大学, 医学部附属病院, 非常勤診療医師 (00452897) ; 宮本 裕士 熊本大学, 医学部附属病院, 講師 (80551259) ; 林 洋光 熊本大学, 医学部附属病院, 非常勤診療医師 (80625773)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: エピジェネティクス / miRNA（キーワード3） / メチル化 / 食道扁平上皮癌 / miRNA / エピジェネティック

Outline of Final Research Achievements

DNA methylation change is common epigenetic change in cancer. The promoter CpG island hypermethylation is one of the most common mechanisms by which tumor suppressor miRNAs are inactivated during tumorigenesis. However, microRNA (miRNA) regulations by epigenetic alteration, especially CpG island hypermethylation, have been not yet substantially understood in esophageal squamous cell carcinoma (ESCC). Therefore, we performed the screening of miRNAs which should be up-regulated by DNA methylation in ESCC cell lines, then from up-regulated miRNAs, we focused on several miRs. Since miRNA-145-5p attracts an increasing attention as a tumor suppressor miRNA in ESCC, we evaluated miRNA-145 promoter methylation level and miRNA-145-5p expression level in ESCC. We evaluated expression level of miR-146a、miR-142、miR-155. However, these expression levels were not associated with clinical feature, including prognosis. Therefore, we could not identify miRNA which regulate malignant behavior of ESCC.

Research Products

• [Journal Article] Prognostic value of LINE-1 methylation level in 321 patients with primary liver cancer including hepatocellular carcinoma and intrahepatic cholangiocarcinoma. (2018)
  • Author(s): Miyata T, Yamashita Y, Baba Y, Harada K, Yamao T, Umezaki N, Tsukamoto M, Kitano Y, Yamamura K, Arima K, Nakagawa S, Okabe H, Imai K, Hashimoto D, Chikamoto A, Shimokawa M, Baba H
  • Journal Title: Oncotarget Volume: 9 Issue: 29 Pages: 20795-20806
  • DOI: 10.18632/oncotarget.25124
  • Peer Reviewed / Open Access
• [Journal Article] LINE-1 methylation level and prognosis in pancreas cancer: pyrosequencing technology and literature review. (2017)
  • Author(s): Yamamura K, Kosumi K, Baba Y, Harada K, Gao F, Zhang X, Zhou L, Kitano Y, Arima K, Kaida T, Takeyama H, Higashi T, Imai K, Hashimoto D, Chikamoto A, Tan X, Baba H
  • Journal Title: Surg Today Volume: 47(12) Issue: 12 Pages: 1450-1459
  • DOI: 10.1007/s00595-017-1539-1
  • Peer Reviewed
• [Journal Article] Suppressor microRNA-145 Is Epigenetically Regulated by Promoter Hypermethylation in Esophageal Squamous Cell Carcinoma. (2015)
  • Author(s): 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.
  • Journal Title: Anticancer Res Volume: 35(9) Pages: 4617-24
  • Peer Reviewed