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Anti-miR-17 therapy delays tumorigenesis in MYC-driven hepatocellular carcinoma (HCC)
| Content Provider | Semantic Scholar |
|---|---|
| Author | Dhanasekaran, Renumathy Gabay-Ryan, Meital Baylot, Virginie Lai, Ian Mosley, Adriane R. Huang, Xinqiang Zabludoff, Sonya D. Li, Jian Kaimal, Vivek Karmali, Priya P. Felsher, Dean W. |
| Copyright Year | 2017 |
| Abstract | Hepatocellular carcinoma (HCC) remains a significant clinical challenge with few therapeutic options. Genomic amplification and/or overexpression of the MYC oncogene is a common molecular event in HCC, thus making it an attractive target for drug therapy. Unfortunately, currently there are no direct drug therapies against MYC. As an alternative strategy, microRNAs regulated by MYC may be downstream targets for therapeutic blockade. MiR-17 family is a microRNA family transcriptionally regulated by MYC and it is commonly overexpressed in human HCCs. In this study, we performed systemic delivery of a novel lipid nanoparticle (LNP) encapsulating an anti-miR-17 oligonucleotide in a conditional transgenic mouse model of MYC driven HCC. Treatment with anti-miR-17 in vivo, but not with a control anti-miRNA, resulted in significant de-repression of direct targets of miR-17, robust apoptosis, decreased proliferation and led to delayed tumorigenesis in MYC-driven HCCs. Global gene expression profiling revealed engagement of miR-17 target genes and inhibition of key transcriptional programs of MYC, including cell cycle progression and proliferation. Hence, anti-miR-17 is an effective therapy for MYC-driven HCC. |
| Starting Page | 5517 |
| Ending Page | 5528 |
| Page Count | 12 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.oncotarget.com/index.php?journal=oncotarget&op=download&page=article&path%5B%5D=22342&path%5B%5D=70691 |
| PubMed reference number | 29464015 |
| Alternate Webpage(s) | https://doi.org/10.18632/oncotarget.22342 |
| DOI | 10.18632/oncotarget.22342 |
| Journal | Oncotarget |
| Volume Number | 9 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Artificial nanoparticles Carcinogenesis Cell Cycle Progression Gene Expression Profiling HCCS gene Lipid Metabolism Disorders Liver carcinoma Liver diseases Liver neoplasms MIR17 wt Allele Mice, Transgenic MicroRNAs Oncogenes Patients Pharmacotherapy Proto-Oncogene Proteins c-myc Repression, Psychology Subgroup A Nepoviruses Therapeutic procedure Transcription, Genetic |
| Content Type | Text |
| Resource Type | Article |
