The Role of Epigenetics and Long Noncoding RNA MIAT in Neuroendocrine Prostate Cancer

Abstract

Neuroendocrine prostate cancer (NEPC) is the most lethal prostatic neoplasm. NEPC is thought to originate from the transdifferentiation of AR-positive adenocarcinoma cells. We have previously shown that an epigenetic/noncoding interactome (ENI) orchestrates cancer cells’ plasticity, thereby allowing the emergence of metastatic, drug-resistant neoplasms. The primary objective of this manuscript is to discuss evidence indicating that some components of the ENI (Polycomb genes, miRNAs) play a key role in NEPC initiation and progression. Long noncoding RNAs represent vast and largely unexplored component of the ENI. Their role in NEPC has not been investigated. We show preliminary evidence indicating that a lncRNA (MIAT) is selectively upregulated in NEPCs and might interact with Polycomb genes. Our results indicate that long noncoding RNAs can be exploited as new biomarkers and therapeutic targets for NEPC.

Keywords::

• epigenetic/noncoding interactome
• long noncoding RNAs
• MIAT
• neuroendocrine prostate cancer
• Polycomb
• transdifferentiation

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/epi.16.6

Financial & competing interests disclosure

This work was financially supported by Canadian Institutes of Health Research, grant numbers: 102604-1, 119991-1, 123449-1 (YZW); Michael Smith Foundation for Health Research Fellowship number 5629 (FC); Prostate Cancer Canada (YZW); Terry Fox Research Institute, grant number: 116129-1 (YZW). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was financially supported by Canadian Institutes of Health Research, grant numbers: 102604-1, 119991-1, 123449-1 (YZW); Michael Smith Foundation for Health Research Fellowship number 5629 (FC); Prostate Cancer Canada (YZW); Terry Fox Research Institute, grant number: 116129-1 (YZW). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.