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

被引：39

作者：

Liao, Tsai-Tsen ^{[1
]}

Hsu, Wen-Hao ^{[1
]}

Ho, Chien-Hsin ^{[1
]}

Hwang, Wei-Lun ^{[7
]}

Lan, Hsin-Yi ^{[1
]}

Lo, Ting ^{[1
]}

Chang, Cheng-Chi ^{[8
]}

Tai, Shyh-Kuan ^{[2
]}

Yang, Muh-Hwa ^{[1
,3
,4
,5
,6
]}

机构：

[1] Natl Yang Ming Univ, Inst Clin Med, 155,Sect 2,Li Nong St, Taipei 11221, Taiwan

[2] Taipei Vet Gen Hosp, Dept Otolaryngol, 201,Sect 2,Shih Pai Rd, Taipei 11217, Taiwan

[3] Natl Yang Ming Univ, Inst Biotechnol Med, 155,Sect 2,Li Nong St, Taipei 11221, Taiwan

[4] Natl Yang Ming Univ, Genom Res Ctr, 155,Sect 2,Li Nong St, Taipei 11221, Taiwan

[5] Taipei Vet Gen Hosp, Dept Oncol, Div Med Oncol, 201,Sect 2,Shih Pai Rd, Taipei 11217, Taiwan

[6] Acad Sinica, Genom Res Ctr, 128,Sect 2,Acad Rd, Taipei 11529, Taiwan

[7] Taipei Med Univ, Coll Med Sci & Technol, Program Translat Med, 250 Wuxing St, Taipei 11031, Taiwan

[8] Natl Taiwan Univ, Sch Dent, Grad Inst Oral Biol, 1,Changde St, Taipei 10048, Taiwan

来源：

CELL REPORTS | 2016年 / 14卷 / 03期

关键词：

SELF-RENEWAL; CANCER; EXPRESSION; CELLS;

D O I：

10.1016/j.celrep.2015.12.064

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

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.

引用

页码：520 / 533

页数：14

共 32 条

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