let-7 Modulates Chromatin Configuration and Target Gene Repression through Regulation of the ARID3B Complex
Open accessAbstract
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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The three selected miRNAs-hsa-miR-122-5p, hsa-let-7a-5p, and hsa-miR-26a-5p-provide complementary and comprehensive coverage of almost all critical genes associated with the MAPK signaling pathway.
“From this analysis, we selected the three abundant miRNAs-hsa-miR-122-5p, hsa-let-7a-5p, and hsa-miR26a-5p-based on their complementary and comprehensive coverage of almost all the critical genes associated with the MAPK signaling pathway 27-33 as analyzed using miRTarBase version 8.0 and TarBase v8.0 integrated within miRNet (Figure S1).”
From rAAV-mediated Multi-miRNA Delivery Targeting MAPK Pathway Suppresses Laser-induced Choroidal Neovascularization in Mice (2026) · cites this paper as [29]
let-7a-5p inhibits EMT and reduces fibrosis.
“It has been reported to inhibit EMT and reduce fibrosis, both of which are crucial factors in the progression of AMD.”
From rAAV-mediated Multi-miRNA Delivery Targeting MAPK Pathway Suppresses Laser-induced Choroidal Neovascularization in Mice (2026) · cites this paper as [29]
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References 34 · Cited by 53
- Authors
- 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.
- Affiliations
- National Yang Ming University (TW)
- Taipei Medical University (TW)
- National Taiwan University (TW)
- Taipei Veterans General Hospital (TW)
- Corresponding author
- Yang, Muh-Hwa
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 14
- Issue
- 3
- Pages
- 520-533
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2237104849
- Cited by
- 53
- References
- 34
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 9 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 8 · 2018: 5 · 2017: 4 · 2016: 1
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Ministry of Science and Technology (101-2314-B-010-021-MY3, 103-2314-B-010-034-MY3, 103-2314-B-010-035-MY3, 103-2321-B-002-020, 103-2633-H-010-001, 104-0210-01-09-02, 104-2321-B-010-005)
- National Health Research Institutes (NHRI-EX104-10331BI)
- Taipei Veterans General Hospital (V104-C-040, V104-E8-001)
- Ministry of Education
- Ministry of Health and Welfare
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- let-7 microRNA, ARID3B, ARID3A, chromatin structure, H3K9 trimethylation, transcriptional repression, cancer stemness, tumor initiation, head and neck cancer, stem cell differentiation, tumor suppression
- MeSH terms
- Animals, Base Sequence, Cell Line, Chromatin, DNA-Binding Proteins, Female, Histones, Humans, Mice, Inbred BALB C, Mice, Nude, Neoplasms, Transcription Factors, Transplantation, Heterologous, Oligonucleotides, Antisense, Sequence Alignment, Karyopherins, RNA Interference, MicroRNAs, Octamer Transcription Factor-3, Mice, Transcriptome
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