NEAT1, a Novel Therapeutic Target and Prognostic Biomarker for Prostate Cancer
- 详细技术说明
- This invention provides methods to treat prostate cancer usinginterfering RNA molecule targeting nuclear enriched abundant transcript 1 (NEAT1)and also methods to use NEAT1 as a biomarker for the diagnosis and prognosis ofprostate cancer.
- *Abstract
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The androgenreceptor (AR) plays a central role in the progression of prostate cancer. Androgen ablation is highly effective intreating metastatic prostate cancer. However, resistance inevitably develops leading to castrate-resistanceprostate cancer (CRPC). How CRPC tumorsbypass AR signaling is emerging as a significant area of investigation.
Recent studiesindicated that estrogen receptor (ER) signaling through ER alpha (ERα)increases with prostate cancer progression. However, the role of ERα remained elusive. Using a combination ofchromatin immunoprecipitation (CHIP) and RNA-sequencing data, Dr. Mark Rubin’slaboratory at Weill Cornell Medicine identified an ERα-specific non-codingtranscriptome signature. They identifiedthat nuclear enriched abundant transcript 1 (NEAT1) is the most significantlyoverexpressed long non-coding RNA (lncRNA) in prostate cancer and is a mediatorof ERα signaling in prostate cancer cells.
They discoveredthat NEAT1 is a transcription regulator and promotes prostate tumorigenesis bygenerating an epigenetic “on” state of downstream prostate cancer specificsignature genes. Knockdown of NEAT1decreases proliferation and the invasive properties of the cells. In xenograft studies of the NOD-SCID mice,tumor growth was found to be significantly lower in the NEAT1 siRNA-expressinggroup. Their studies demonstrate thattargeting NEAT1 is an alternative strategy to treat prostate cancer,particularly useful for treating a patient having an advanced stage prostatecancer.
The researchers also analyzed two large clinicalcohorts and revealed that NEAT1 is associated with prostate cancer progression. Prostate cancer cells expressing high levelsof NEAT1 were recalcitrant to androgen or AR antagonist. These results show that NEAT1 is a diagnosticand prognostic biomarker for prostate cancer.
Potential Applications
- Treating prostate cancer using interfering RNA molecule(e.g. siRNA, miRNA and shRNA) targeting NEAT1
- A diagnostic and prognostic biomarker for prostate cancer
Advantages
- A novel therapeutic strategy targeting a signaling axis independenton the androgen/androgen receptor pathway
- A potential candidate for co-targeting therapies to treatprostate cancer
- Mayuse tissue, urine, blood, semen , prostatic secretions or prostate cells fordiagnosis and prognosis
- *Licensing
- Brian J. Kellybjk44@cornell.edu212-746-6186
- 其他
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The oestrogen receptoralpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer. Nat Commun., 2014, 5, 5383. PMID:25415230.
- 国家/地区
- 美国
