Expression analysis of miRNAs regulated by EZH2 in adult T-cell leukemia

Research Project

Project/Area Number	25860411
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Laboratory medicine
Research Institution	Nagasaki University
Principal Investigator	SASAKI Daisuke 長崎大学, 病院(医学系), 技術職員 (90624784)
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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000) Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	ATL / EZH2 / miRNA / HTLV-1
Outline of Final Research Achievements	MiR-181a was re-expressed in ATL cells by EZH2 inhibitor DZNep, which activated capase3/7 and induced apoptosis in ATL cells. MiR-181a has been shown to be regulated by EZH2, while miR-181a is a candidate negative regulator of BCL2 expression. We confirmed that BCL2 mRNA and protein expressions were clearly suppressed in the ATL cell lines by DZNep. DZNep inhibits cell growth that is caused BCL2 repression via miR-181a. These results strongly support the notion that miR-181a is suppressed by EZH2 and that BCL2 expression is regulated by miR-181a in ATL cells. Together, our findings indicate a unique apoptotic pathway of BCL2 suppression via miR181a and that the EZH2 inhibitor DZNep may become a novel therapeutic agent for ATL.