ArticleCell death & disease2020
Comp34 displays potent preclinical antitumor efficacy in triple-negative breast cancer via inhibition of NUDT3-AS4, a novel oncogenic long noncoding RNA.
Article in Cell death & disease, 2020. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Advances of androgen receptor in triple-negative breast cancer: from molecular mechanisms to clinical applications.Discover oncology · 2025Review
- Investigating the role of exosomal long non-coding RNAs in drug resistance within female reproductive system cancers.Frontiers in cell and developmental biology · 2025Review
- Pre-diagnosis blood DNA methylation profiling of twin pairs discordant for breast cancer points to the importance of environmental risk factors.Clinical epigenetics · 2024Article
- Impact of microRNA variants on PI3K/AKT signaling in triple-negative breast cancer: comprehensive review.Medical oncology (Northwood, London, England) · 2024Review
- SP1-Induced Upregulation of LncRNA AFAP1-AS1 Promotes Tumor Progression in Triple-Negative Breast Cancer by Regulating mTOR Pathway.International journal of molecular sciences · 2023Article
- Long Non-Coding RNAs, Cell Cycle, and Human Breast Cancer.Human gene therapy · 2023Review
- Interplay between LncRNAs and microRNAs in Breast Cancer.International journal of molecular sciences · 2023Review
- Nanomaterial-assisted CRISPR gene-engineering - A hallmark for triple-negative breast cancer therapeutics advancement.Materials today. Bio · 2022Review
- Construction of N-7 methylguanine-related mRNA prognostic model in uterine corpus endometrial carcinoma based on multi-omics data and immune-related analysis.Scientific reports · 2022Article
- Long non-coding RNAs and cancer mechanisms: Immune cells and inflammatory cytokines in the tumor microenvironment.Medical oncology (Northwood, London, England) · 2022Review
- The Mechanisms of lncRNA-Mediated Multidrug Resistance and the Clinical Application Prospects of lncRNAs in Breast Cancer.Cancers · 2022Review
- Curcuminoids as Modulators of EMT in Invasive Cancers: A Review of Molecular Targets With the Contribution of Malignant Mesothelioma Studies.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) AL354740.1-204 (also named as NUDT3-AS4) acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression. Inhibition of lncRNA-NUDT3-AS4 and suppression of the NUDT3-AS4/miR-99s association contribute to Comp34-affected biologic pathways. In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. In conclusion, NUDT3-AS4 may play a proproliferative role in TNBC and be considered a relevant therapeutic target, and Comp34 presents promising activity as a single agent to inhibit TNBC through regulation of NUDT3-AS4 and miR-99s.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.