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Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Oncotarget 2016 ; 7 (16): 22448-59 Nephropedia Template TP
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ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance #MMPMID26968954
Chung IH; Liu H; Lin YH; Chi HC; Huang YH; Yang CC; Yeh CT; Tan BCM; Lin KH
Oncotarget 2016[Apr]; 7 (16): 22448-59 PMID26968954show ga
Triiodothyronine (T3) and its receptor (TR) modulate several physiological processes, including cell development, proliferation, differentiation and metabolism. The regulatory mechanism of T3/TR involves binding to the thyroid hormone response element (TRE) within the target gene promoter. However, the number of target genes directly regulated by TR?1 and the specific pathways of TR-regulated target genes remain largely unknown. Here, we expressed TR?1 in a HepG2 cell line and used chromatin immunoprecipitation coupled with microarray to determine the genes that are directly regulated by TR?1 and also involved in cell metabolism and proliferation. Our analysis identified E74-like factor 2 (ELF2), a transcription factor associated with tumor growth, as a direct target downregulated by T3/TR. Overexpression of ELF2 enhanced tumor cell proliferation, and conversely, its knockdown suppressed tumor growth. Additionally, ELF2 restored the proliferative ability of hepatoma cells inhibited by T3/TR. Our findings collectively support a potential role of T3/TR in tumor growth inhibition through regulation of ELF2.