Identification of a novel tumor-suppressor gene through methylome analysis in smoking-associated lung adenocarcinoma

Research Project

Project/Area Number	25861245
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Respiratory surgery
Research Institution	The University of Tokushima
Principal Investigator	KAJIURA Koichiro 徳島大学, 大学病院, 助教 (60596253)
Project Period (FY)	2013-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000) Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords	肺腺癌 / エピゲノム / メチル化 / 喫煙
Outline of Final Research Achievements	We explored aberrant DNA methylation of lung adenocarcinoma possible to be induced by smoking with surgical specimen. Comprehensive analysis of epigenome alternation showed TRIM58 gene was hypermethylation on promotor region in cancer tissue significantly. It is tendency that hypermethylation in smoker cohort compare to non-smoker cohort. Pyrosequencing showed similar result. Real time RT-PCR showed mRNA expression is lower in cancer tissue than in normal tissue significantly. Immunostaining showed protein expression level is lower in cancer tissue than in normal tissue. We transfected TRIM58 in A549 . Cell count and MTT assay showed cell growth inhabitation in A549 transfected TRIM58. We transplanted this A549 cell line to subcutaneous in SCID mice, The growth of A549 transfected TRIM58 was inhibited significantly. TRIM58 is thoughtto be tumor suppressor gene and inactivated by DNA methylation.