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

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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. Liao et al. find that let-7 regulates target gene expression in cancer cells through regulation of the ARID3B complex, which promotes H3K9 demethylation at target genes. This finding suggests a chromatin-dependent mechanism in let-7-regulated cancer stemness.

Original languageEnglish
JournalCell Reports
DOIs
Publication statusAccepted/In press - Aug 14 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Liao, T. T., Hsu, W. H., Ho, C. H., Hwang, W. L., Lan, H. Y., Lo, T., Chang, C. C., Tai, S. K., & Yang, M. H. (Accepted/In press). Let-7 Modulates Chromatin Configuration and Target Gene Repression through Regulation of the ARID3B Complex. Cell Reports. https://doi.org/10.1016/j.celrep.2015.12.064