Knockdown of SF-1 and RNF31 affects components of steroidogenesis, TGFβ, and Wnt/β-catenin signaling in adrenocortical carcinoma cells.
Knockdown of SF-1 and RNF31 affects components of steroidogenesis, TGFβ, and Wnt/β-catenin signaling in adrenocortical carcinoma cells.
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DOI：
10.1371/journal.pone.0032080
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Treuter E
中科院分区：
文献类型：
--
作者：
Ehrlund A;Jonsson P;Vedin LL;Williams C;Gustafsson JÅ;Treuter E
孤儿核受体类固醇生成因子-1（SF-1，NR 5A 1）是肾上腺皮质和性腺发育和稳态的关键调节因子。我们最近发现，含有E3泛素连接酶RNF 31和已知SF-1辅阻遏物DAX-1（NR 0 B1）的复合物与SF-1在靶启动子上相互作用，并抑制类固醇生成急性调节蛋白（星星）和芳香酶（CYP 19）基因的转录。为了进一步评估SF-1在肾上腺皮质中的作用以及RNF 31在SF-1依赖性通路中的参与，我们对肾上腺皮质NCI-H295 R细胞进行了全基因组基因表达分析，其中SF-1或RNF 31已经使用RNA干扰被敲低。我们发现RNF 31与胆固醇代谢和类固醇激素合成密切相关，加强了其作为SF-1辅助调节因子的作用。我们还发现了SF-1与转化生长因子（TGF）β和Wnt/β-连环蛋白信号传导之间负串扰的有趣证据。这种串扰可能对肾上腺性腺发育、肾上腺皮质祖细胞的维持和肾上腺皮质癌的发展具有重要意义。最后，SF-1基因谱可用于区分恶性和良性肾上腺皮质肿瘤，这一发现暗示SF-1在恶性肾上腺皮质癌的发展。
The orphan nuclear receptor Steroidogenic Factor-1 (SF-1, NR5A1) is a critical regulator of development and homeostasis of the adrenal cortex and gonads. We recently showed that a complex containing E3 ubiquitin ligase RNF31 and the known SF-1 corepressor DAX-1 (NR0B1) interacts with SF-1 on target promoters and represses transcription of steroidogenic acute regulatory protein (StAR) and aromatase (CYP19) genes. To further evaluate the role of SF-1 in the adrenal cortex and the involvement of RNF31 in SF-1-dependent pathways, we performed genome-wide gene-expression analysis of adrenocortical NCI-H295R cells where SF-1 or RNF31 had been knocked down using RNA interference. We find RNF31 to be deeply connected to cholesterol metabolism and steroid hormone synthesis, strengthening its role as an SF-1 coregulator. We also find intriguing evidence of negative crosstalk between SF-1 and both transforming growth factor (TGF) β and Wnt/β-catenin signaling. This crosstalk could be of importance for adrenogonadal development, maintenance of adrenocortical progenitor cells and the development of adrenocortical carcinoma. Finally, the SF-1 gene profile can be used to distinguish malignant from benign adrenocortical tumors, a finding that implicates SF-1 in the development of malignant adrenocortical carcinoma.
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影响因子：
4.8
作者：
Ding, Xunshan;Lichti, Kristin;Staudinger, Jeff L.
通讯作者：
Staudinger, Jeff L.
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
5.3
作者：
Campbell, Lioudmila A.;Faivre, Emily J.;Ingraham, Holly A.
通讯作者：
Ingraham, Holly A.
影响因子：
--
作者：
Hanley, NA;Rainey, WE;Parker, KL
通讯作者：
Parker, KL
影响因子：
45.3
作者：
de Reynies, Aurelien;Assie, Guillaume;Bertherat, Jerome
通讯作者：
Bertherat, Jerome