NEAT1, a Novel Therapeutic Target and Prognostic Biomarker for Prostate Cancer

This invention provides methods to treat prostate cancer using interfering RNA molecule targeting nuclear enriched abundant transcript 1 (NEAT1) and also methods to use NEAT1 as a biomarker for the diagnosis and prognosis of prostate cancer.

Technology Overview

The androgen receptor (AR) plays a central role in the progression of prostate cancer. Androgen ablation is highly effective in treating metastatic prostate cancer. However, resistance inevitably develops leading to castrate-resistance prostate cancer (CRPC). How CRPC tumors bypass AR signaling is emerging as a significant area of investigation.

Recent studies indicated that estrogen receptor (ER) signaling through ER alpha (ERα) increases with prostate cancer progression. However, the role of ERα remained elusive. Using a combination of chromatin immunoprecipitation (CHIP) and RNA-sequencing data, Dr. Mark Rubin’s laboratory at Weill Cornell Medicine identified an ERα-specific non-coding transcriptome signature. They identified that nuclear enriched abundant transcript 1 (NEAT1) is the most significantly overexpressed long non-coding RNA (lncRNA) in prostate cancer and is a mediator of ERα signaling in prostate cancer cells.

They discovered that NEAT1 is a transcription regulator and promotes prostate tumorigenesis by generating an epigenetic “on” state of downstream prostate cancer specific signature genes. Knockdown of NEAT1 decreases 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-expressing group. Their studies demonstrate that targeting NEAT1 is an alternative strategy to treat prostate cancer, particularly useful for treating a patient having an advanced stage prostate cancer.

The researchers also analyzed two large clinical cohorts and revealed that NEAT1 is associated with prostate cancer progression. Prostate cancer cells expressing high levels of NEAT1 were recalcitrant to androgen or AR antagonist. These results show that NEAT1 is a diagnostic and 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 independent on the androgen/androgen receptor pathway
• A potential candidate for co-targeting therapies to treat prostate cancer
• May use tissue, urine, blood, semen , prostatic secretions or prostate cells for diagnosis and prognosis