Regulation of miRNAs located within the imprinted DLK1-DIO3 locus at 14q32 in pituitary adenomas

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09435
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: The University of Tokushima
• Principal Investigator: YOSHIMOTO Katsuhiko 徳島大学, 大学院医歯薬学研究部(歯学系), 教授 (90201863)
• Co-Investigator(Kenkyū-buntansha): 岩田 武男 徳島大学, 大学院医歯薬学研究部(歯学系), 助教 (10350399) ; 水澤 典子 徳島大学, 大学院医歯薬学研究部(歯学系), 助教 (80254746)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 下垂体 / 腫瘍 / インプリンティング / DNAメチル化

Outline of Final Research Achievements

Among miRNAs up-regulated in GH-producing adenomas in miRNA microarray analysis, 14q32 miRNAs were included. In contrast, these miRNAs were down-regulated in FSH/LH- and ACTH-producing adenomas, and null-cell adenomas. The adenoma type-dependent expression pattern was confirmed with qRT-PCR analysis. Although DNA copy-number changes at the 14q32 locus were not detected in all adenomas examined, abnormal methylation of CpG sites in imprinted genes within the DLK1-DIO3 locus was observed in 2 GH-producing adenomas by methylation-specific MLPA. According to DNA methylation analysis by pyrosequencing and bisulfite sequencing, methylation levels were different at each individual CpG site in intergenic DMR and MEG3-DMR, which regulate maternal gene expression at the DLK1-DIO3 locus, in 2 GH-producing adenomas. In conclusion, 14q32 miRNAs were up-regulated in sporadic GH-producing adenomas and methylation abnormalities were observed in certain GH-producing adenomas.

Free Research Field

内分泌学・代謝学