ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
The miR-5694/AF9/Snail Axis Provides Metastatic Advantages and a Therapeutic Target in Basal-like Breast Cancer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Innovative Approaches to EMT-Related Biomarker Identification in Breast Cancer: Multi-Omics and Machine Learning Methods.Biotech (Basel (Switzerland)) · 2025Review
- MLLT3 Regulates Melanoma Stemness and Progression by Inhibiting HMGB1 Nuclear Entry and MAGEA1 MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Noncoding RNAs, Vital Players in Breast Cancer Metastasis.Breast cancer (Dove Medical Press) · 2025Review
- Unveiling the role of GAS41 in cancer progression.Cancer cell international · 2023Review
- AF9 sustains glycolysis in colorectal cancer via H3K9ac-mediated PCK2 and FBP1 transcription.Clinical and translational medicine · 2023Article
- Hub gene of disulfidptosis-related immune checkpoints in breast cancer.Medical oncology (Northwood, London, England) · 2023Article
- AF9 targets acetyl-modified STAT6 to diminish purine metabolism and accelerate cell apoptosis during metastasis.Cell death and differentiation · 2023Article
- Circular RNA hsa_circ_0004689 (circSWT1) promotes NSCLC progression via the miR-370-3p/SNAIL axis by inducing cell epithelial-mesenchymal transition (EMT).Cancer medicine · 2023Article
- A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation.Nutrients · 2021Article
- Construction of a Myc-associated ceRNA network reveals a prognostic signature in hepatocellular carcinoma.Molecular therapy. Nucleic acids · 2021Article
- Comprehensive analysis to identify DLEU2L/TAOK1 axis as a prognostic biomarker in hepatocellular carcinoma.Molecular therapy. Nucleic acids · 2021Article
- A New Strategy to Identify ceRNA-Based CCDC144NL-AS1/SERPINE1 Regulatory Axis as a Novel Prognostic Biomarker for Stomach AdenocarcinomaFrontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epigenetic deregulation, especially mutagenesis or the abnormal expression of epigenetic regulatory factors (ERFs), plays an important role in malignant tumorigenesis. To screen natural inhibitors of breast cancer metastasis, we adopted small interfering RNAs (siRNAs) to transiently knock down 591 ERF-coding genes in luminal breast cancer MCF-7 cells and found that depletion of AF9 significantly promoted MCF-7 cell invasion and migration. A mouse model of metastasis further confirmed the suppressive role of AF9 in breast cancer metastasis. RNA profiling revealed enrichment of AF9 targets genes in the epithelial-mesenchymal transition (EMT). Mechanistically, tandem mass spectrometry showed that AF9 interacts with Snail, which hampers Snail transcriptional activity in basal-like breast cancer (BLBC) cells. AF9 reconstitutes an activated state on the promoter of Snail, which is a master regulator of EMT, and derepresses genes by recruiting CBP or GCN5. Additionally, microRNA-5694 (miR-5694) targeted and degraded AF9 messenger RNA (mRNA) in BLBC cells, further enhancing cell invasion and migration. Notably, AF9 and miR-5694 expression in BLBC clinical samples correlated inversely. Hence, miR-5694 mediates downregulation of AF9 and provides metastatic advantages in BLBC. Restoring expression of the metastasis suppressor AF9 is a possible therapeutic strategy against metastatic breast cancer.
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