HOX genes promote cell proliferation and are potential therapeutic targets in adrenocortical tumours.
HOX genes promote cell proliferation and are potential therapeutic targets in adrenocortical tumours.
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HOX基因促进细胞增殖，是肾上腺皮质肿瘤的潜在治疗靶点。
DOI：
10.1038/s41416-020-01166-z
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发表时间：
2021-03
影响因子：
8.8
通讯作者：
Swain A
中科院分区：
文献类型：
--
作者：
Francis JC;Gardiner JR;Renaud Y;Chauhan R;Weinstein Y;Gomez-Sanchez C;Lefrançois-Martinez AM;Bertherat J;Val P;Swain A
了解驱动肾上腺皮质癌（ACC）的途径对于开发更有效的治疗方法至关重要。本研究探讨了转录因子HOXB 9和其他HOX因子在ACC及其治疗中的作用。我们使用转基因小鼠模型来确定Hoxb9在肾上腺肿瘤发展中的作用。分析患者转录组数据的HOX基因表达及其与疾病的相关性。对各种肾上腺皮质模型进行药物反应研究，以建立新的治疗选择。我们的人类ACC数据集分析显示，HOXB 9和其他HOX因子的高表达与较差的预后相关。在Ctnnb 1激活的小鼠肾上腺皮质中Hoxb9的转基因过表达导致更大的肾上腺肿瘤。这种表型优先在雄性小鼠中观察到，其特征在于更多的增殖细胞和细胞周期基因（包括Ccne1）表达的增加。肾上腺肿瘤细胞被发现依赖于HOX功能的生存和敏感的特定肽抑制剂。这些研究表明，Hoxb9可以以性别依赖的方式促进肾上腺肿瘤的进展，并将HOX因子确定为潜在的药物靶点，从而为ACC提供了新的治疗方法。
Understanding the pathways that drive adrenocortical carcinoma (ACC) is essential to the development of more effective therapies. This study investigates the role of the transcription factor HOXB9 and other HOX factors in ACC and its treatment. We used transgenic mouse models to determine the role of Hoxb9 in adrenal tumour development. Patient transcriptomic data was analysed for the expression of HOX genes and their association with disease. Drug response studies on various adrenocortical models were done to establish novel therapeutic options. Our human ACC dataset analyses showed high expression of HOXB9, and other HOX factors, are associated with poorer prognosis. Transgenic overexpression of Hoxb9 in the adrenal cortex of mice with activated Ctnnb1 led to larger adrenal tumours. This phenotype was preferentially observed in male mice and was characterised by more proliferating cells and an increase in the expression of cell cycle genes, including Ccne1. Adrenal tumour cells were found to be dependent on HOX function for survival and were sensitive to a specific peptide inhibitor. These studies show Hoxb9 can promote adrenal tumour progression in a sex-dependent manner and have identified HOX factors as potential drug targets, leading to novel therapeutic approaches in ACC.
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影响因子：
5.5
作者：
Gao, Dong;Chen, Hong-Quan
通讯作者：
Chen, Hong-Quan
影响因子：
3.5
作者：
Berthon, Annabel;Sahut-Barnola, Isabelle;Val, Pierre
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Guo, Jiankuo;Zhang, Tianlun;Dou, Dongmei
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作者：
Juhlin, C. Christofer;Goh, Gerald;Carling, Tobias
通讯作者：
Carling, Tobias
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4.5
作者：
Francis JC;Thomsen MK;Taketo MM;Swain A
通讯作者：
Swain A