ArticleScientific reports2015
Targeted Regression of Hepatocellular Carcinoma by Cancer-Specific RNA Replacement through MicroRNA Regulation.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- miR-19-3p Targets PTEN to Regulate Cervical Cancer Cell Proliferation, Invasion, and Autophagy.Genetics research · 2023Article
- Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells.Nature biotechnology · 2022Article
- Non-Canonical Splicing and Its Implications in Brain Physiology and Cancer.International journal of molecular sciences · 2022Review
- RNA Therapeutic Options to Manage Aberrant Signaling Pathways in Hepatocellular Carcinoma: Dream or Reality?Frontiers in oncology · 2022Review
- The Emerging Factors and Treatment Options for NAFLD-Related Hepatocellular Carcinoma.Cancers · 2021Review
- Targeted suicide gene therapy for liver cancer based on ribozyme-mediated RNA replacement through post-transcriptional regulation.Molecular therapy. Nucleic acids · 2021Article
- Therapeutic applications of trans-splicing.British medical bulletin · 2020Article
- Neoadjuvant Use of Oncolytic Herpes Virus G47Δ Enhances the Antitumor Efficacy of Radiofrequency Ablation.Molecular therapy oncolytics · 2020Article
- Circular RNA ABCB10 promotes hepatocellular carcinoma progression by increasing HMG20A expression by sponging miR-670-3p.Cancer cell international · 2019Article
- Synergistic and independent action of endogenous microRNAs 122a and 199a for post-transcriptional liver detargeting of gene vectors.Scientific reports · 2018Article
- miRNA122a regulation of gene therapy vectors targeting hepatocellular cancer stem cells.Oncotarget · 2018Article
- Suppression of miR-22, a tumor suppressor in cervical cancer, by human papillomavirus 16 E6 via a p53/miR-22/HDAC6 pathway.PloS one · 2018Article
- Specific and Efficient Regression of Cancers Harboring KRAS Mutation by Targeted RNA Replacement.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- MicroRNA-regulated viral vectors for gene therapy.World journal of experimental medicine · 2016Review
- Article
- Telomerase Expression Related with Poor Immune Response to HCV Core Antigen in Egyptian HCV Patients' PBMCs.Journal of clinical and experimental hepatologyArticle
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) has a high fatality rate and limited therapeutic options with side effects and low efficacy. Here, we proposed a new anti-HCC approach based on cancer-specific post-transcriptional targeting. To this end, trans-splicing ribozymes from Tetrahymena group I intron were developed, which can specifically induce therapeutic gene activity through HCC-specific replacement of telomerase reverse transcriptase (TERT) RNA. To circumvent side effects due to TERT expression in regenerating liver tissue, liver-specific microRNA-regulated ribozymes were constructed by incorporating complementary binding sites for the hepatocyte-selective microRNA-122a (miR-122a), which is down-regulated in HCC. The ribozyme activity in vivo was assessed in mouse models orthotopically implanted with HCC. Systemic administration of adenovirus encoding the developed ribozymes caused efficient anti-cancer effect and the least hepatotoxicity with regulation of ribozyme expression by miR-122a in both xenografted and syngeneic orthotopic murine model of multifocal HCC. Of note, the ribozyme induced local and systemic antitumor immunity, thereby completely suppressing secondary tumor challenge in the syngeneic mouse. The cancer specific trans-splicing ribozyme system, which mediates tissue-specific microRNA-regulated RNA replacement, provides a clinically relevant, safe, and efficient strategy for HCC treatment.
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