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

Cell Reports
Tsai-Tsen LiaoMuh-Hwa Yang

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.

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Citations

Dec 2, 2017·Nucleic Acids Research·Tomas TokarIgor Jurisica
Jan 13, 2018·PLoS Genetics·Baolu ShiP Jeremy Wang
Jun 22, 2019·Genes & Development·Saifeng WangStefan A Muljo
Aug 16, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Asghar AliQuinton A Winger
May 28, 2020·International Journal of Molecular Sciences·Asghar AliQuinton A Winger
Apr 18, 2018·Cancer Growth and Metastasis·Lynn RoyKaren D Cowden Dahl
Apr 25, 2018·Journal of Biomedical Science·San-Chi ChenMuh-Hwa Yang
May 1, 2021·Cancers·Melysa FitrianaTsai-Tsen Liao
Jul 3, 2021·Biomolecules·Jacek KabzinskiIreneusz Majsterek

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