ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
Knockdown of β-catenin with dicer-substrate siRNAs reduces liver tumor burden in vivo.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 57 citations in OpenAlex.
- Programmable protein degraders enable selective knockdown of pathogenic β-catenin subpopulations in vitro and in vivo.Science advances · 2026Article
- Recent Advances in RNA Interference-Based Therapy for Hepatocellular Carcinoma: Emphasis on siRNA.Cell biochemistry and biophysics · 2024Review
- Membrane-Cloaked Nanoparticles for RNA Interference of β-Catenin in Triple-Negative Breast Cancer.ACS biomaterials science & engineering · 2024Article
- Therapeutic RNA interference: A novel approach to the treatment of primary hyperoxaluria.British journal of clinical pharmacology · 2022Review
- Article
- Direct targeting of β-catenin in the Wnt signaling pathway: Current progress and perspectives.Medicinal research reviews · 2021Review
- Review
- Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance.Cancers · 2021Review
- Astrocyte elevated gene-1 (AEG-1): A key driver of hepatocellular carcinoma (HCC).Advances in cancer research · 2021Review
- Lipid Delivery Systems for Nucleic-Acid-Based-Drugs: From Production to Clinical Applications.Pharmaceutics · 2019Review
- Frontal Bone Healing Is Sensitive to Wnt Signaling Inhibition via Lentiviral-Encoded Beta-Catenin Short Hairpin RNA.Tissue engineering. Part A · 2018Article
- β-Catenin mRNA Silencing and MEK Inhibition Display Synergistic Efficacy in Preclinical Tumor Models.Molecular cancer therapeutics · 2018Article
- Oncogenic dependency on β-catenin in liver cancer cell lines correlates with pathway activation.Oncotarget · 2017Article
- Profiling the Mismatch Tolerance of Argonaute 2 through Deep Sequencing of Sliced Polymorphic Viral RNAs.Molecular therapy. Nucleic acids · 2017Article
- Direct Pharmacological Inhibition of β-Catenin by RNA Interference in Tumors of Diverse Origin.Molecular cancer therapeutics · 2016Article
- Current development of targeted oligonucleotide-based cancer therapies: Perspective on HER2-positive breast cancer treatment.Cancer treatment reviews · 2016Review
- Inhibition of Glycolate Oxidase With Dicer-substrate siRNA Reduces Calcium Oxalate Deposition in a Mouse Model of Primary Hyperoxaluria Type 1.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Cellular localization of long non-coding RNAs affects silencing by RNAi more than by antisense oligonucleotides.Nucleic acids research · 2016Article
- Iron-Oxide-Based Nanovector for Tumor Targeted siRNA Delivery in an Orthotopic Hepatocellular Carcinoma Xenograft Mouse Model.Small (Weinheim an der Bergstrasse, Germany) · 2016Article
- High Expression of the Newly Found Long Noncoding RNA Z38 Promotes Cell Proliferation and Oncogenic Activity in Breast Cancer.Journal of Cancer · 2016Article
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite progress in identifying molecular drivers of cancer, it has been difficult to translate this knowledge into new therapies, because many of the causal proteins cannot be inhibited by conventional small molecule therapeutics. RNA interference (RNAi), which uses small RNAs to inhibit gene expression, provides a promising alternative to reach traditionally undruggable protein targets by shutting off their expression at the messenger RNA (mRNA) level. Challenges for realizing the potential of RNAi have included identifying the appropriate genes to target and achieving sufficient knockdown in tumors. We have developed high-potency Dicer-substrate short-interfering RNAs (DsiRNAs) targeting β-catenin and delivered these in vivo using lipid nanoparticles, resulting in significant reduction of β-catenin expression in liver cancer models. Reduction of β-catenin strongly reduced tumor burden, alone or in combination with sorafenib and as effectively as DsiRNAs that target mitotic genes such as PLK1 and KIF11. β-catenin knockdown also strongly reduced the expression of β-catenin-regulated genes, including MYC, providing a potential mechanism for tumor inhibition. These results validate β-catenin as a target for liver cancer therapy and demonstrate the promise of RNAi in general and DsiRNAs in particular for reaching traditionally undruggable cancer targets.
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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.