ArticleMolecular therapy. Nucleic acids2019
Bioengineered Let-7c Inhibits Orthotopic Hepatocellular Carcinoma and Improves Overall Survival with Minimal Immunogenicity.
Article in Molecular therapy. Nucleic acids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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
35 citing papers in PubMed, 1 synthesis or guideline pooled it.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Bioengineered miR-148a-3p suppresses glycolysis and amino acid homeostasis in hepatocellular carcinoma cells by regulating multiple solute carrier transporters.Liver research (Beijing, China) · 2026Article
- Comparative effectiveness of 7 major human let-7-5p isoforms to modulate target gene expression in liver cells.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Unraveling the influence of TGF-β rs9282871 and miRNA let-7c relative expression on TGF-β production in hepatocellular carcinoma patients.Journal, genetic engineering & biotechnology · 2026Article
- Efficiency and safety of five different agents forFrontiers in molecular biosciences · 2026Article
- Comparison of Three Computational Tools for the Prediction of RNA Tertiary Structures.Non-coding RNA · 2024Article
- Molecular Engineering of Functional SiRNA Agents.ACS synthetic biology · 2024Article
- Novel RNA molecular bioengineering technology efficiently produces functional miRNA agents.RNA (New York, N.Y.) · 2024Article
- Role of ABCC5 in cancer drug resistance and its potential as a therapeutic target.Frontiers in cell and developmental biology · 2024Review
- Efflux ABC transporters in drug disposition and their posttranscriptional gene regulation by microRNAs.Frontiers in pharmacology · 2024Review
- Use of recombinant microRNAs as antimetabolites to inhibit human non-small cell lung cancer.Acta pharmaceutica Sinica. B · 2023Article
- Recombinant Technologies Facilitate Drug Metabolism, Pharmacokinetics, and General Biomedical Research.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies.The Journal of pharmacology and experimental therapeutics · 2023Review
- Let-7c-5p Restrains Cell Growth and Induces Apoptosis of Lung Adenocarcinoma Cells via Targeting ESPL1.Molecular biotechnology · 2022Article
- Bioengineered miR-34a modulates mitochondrial inner membrane protein 17 like 2 (MPV17L2) expression toward the control of cancer cell mitochondrial functions.Bioengineered · 2022Article
- Exosomes of A549 Cells Induced Migration, Invasion, and EMT of BEAS-2B Cells Related to let-7c-5p and miR-181b-5p.Frontiers in endocrinology · 2022Article
- Bioengineered RNA Therapy in Patient-Derived Organoids and Xenograft Mouse Models.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Polyethyleneimine-Based Lipopolyplexes as Carriers in Anticancer Gene Therapies.Materials (Basel, Switzerland) · 2021Review
- Bioengineered miR-124-3p prodrug selectively alters the proteome of human carcinoma cells to control multiple cellular components and lung metastasisActa pharmaceutica Sinica. B · 2021Article
- Single bioengineered ncRNA molecule for dual-targeting toward the control of non-small cell lung cancer patient-derived xenograft tumor growth.Biochemical pharmacology · 2021Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths, warranting better therapies. Restoration of tumor-suppressive microRNAs depleted in hepatocellular carcinoma represents a new therapeutic strategy. Herein, we sought to identify a potent microRNA (miRNA) agent that could alleviate HCC tumor burden and improve survival. Among a collection of bioengineered noncoding RNA molecules produced through bacterial fermentation, we identified let-7c agent as the most potent inhibitor of HCC cell viability. Bioengineered let-7c selectively modulated target gene expression (Lin-28 homolog B [LIN28B], AT-rich interactive domain-containing protein 3B [ARID3B], B cell lymphoma-extra large [Bcl-xl], and c-Myc) in HCC cells, and consequently induced apoptosis and inhibited tumorsphere growth. When formulated with liposomal-branched polyethylenimine polyplex, bioengineered let-7c exhibited serum stability up to 24 h. Furthermore, liposomal polyplex-formulated let-7c could effectively reduce tumor burden and progression in orthotopic HCC mouse models, while linear polyethyleneimine-formulated let-7c to a lower degree, as revealed by live animal and ex vivo tissue imaging studies. This was also supported by reduced serum α-fetoprotein and bilirubin levels in let-7c-treated mice. In addition, lipopolyplex-formulated let-7c extended overall survival of HCC tumor-bearing mice and elicited no or minimal immune responses in healthy immunocompetent mice and human peripheral blood mononuclear cells. These results demonstrate that bioengineered let-7c is a promising molecule for advanced HCC therapy, and liposomal polyplex is a superior modality for in vivo RNA delivery.
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Registered trials
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