Let-7 Modulates Chromatin Configuration and Target Gene Repression through Regulation of the ARID3B Complex

Tsai Tsen Liao, Wen Hao Hsu, Chien Hsin Ho, Wei Lun Hwang, Hsin Yi Lan, Ting Lo, Cheng Chi Chang, Shyh Kuan Tai, Muh Hwa Yang*

*此作品的通信作者

研究成果: Article同行評審

42 引文 斯高帕斯(Scopus)

摘要

Let-7 is crucial for both stem cell differentiation and tumor suppression. Here, we demonstrate a chromatin-dependent mechanism of let-7 in regulating target gene expression in cancer cells. Let-7 directly represses the expression of AT-rich interacting domain 3B (ARID3B), ARID3A, and importin-9. In the absence of let-7, importin-9 facilitates the nuclear import of ARID3A, which then forms a complex with ARID3B. The nuclear ARID3B complex recruits histone demethylase 4C to reduce histone 3 lysine 9 trimethylation and promotes the transcription of stemness factors. Functionally, expression of ARID3B is critical for the tumor initiation in let-7-depleted cancer cells. An inverse association between let-7 and ARID3A/ARID3B and prognostic significance is demonstrated in head and neck cancer patients. These results highlight a chromatin-dependent mechanism where let-7 regulates cancer stemness through ARID3B.

原文English
頁(從 - 到)520-533
頁數14
期刊Cell Reports
14
發行號3
DOIs
出版狀態Published - 26 1月 2016

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