MicroRNAs in treatment-induced neuroendocrine differentiation in prostate cancer

Theresa Akoto, Divya Bhagirath, Sharanjot Saini

Research output: Contribution to journalReview articlepeer-review

Abstract

Prostate cancer is a condition commonly associated with men worldwide. Androgen deprivation therapy remains one of the targeted therapies. However, after some years, there is biochemical recurrence and metastatic progression into castration-resistant prostate cancer (CRPC). CRPC cases are treated with second-line androgen deprivation therapy, after which, these CRPCs transdifferentiate to form neuroendocrine prostate cancer (NEPC), a highly aggressive variant of CRPC. NEPC arises via a reversible transdifferentiation process, known as neuroendocrine differentiation (NED), which is associated with altered expression of lineage markers such as decreased expression of androgen receptor and increased expression of neuroendocrine lineage markers including enolase 2, chromogranin A and synaptophysin. The etiological factors and molecular basis for NED are poorly understood, contributing to a lack of adequate molecular biomarkers for its diagnosis and therapy. Therefore, there is a need to fully understand the underlying molecular basis for this cancer. Recent studies have shown that microRNAs (miRNAs) play a key epigenetic role in driving therapy-induced NED in prostate cancer. In this review, we briefly describe the role of miRNAs in prostate cancer and CRPCs, discuss some key players in NEPCs and elaborate on miRNA dysregulation as a key epigenetic process that accompanies therapy-induced NED in metastatic CRPC. This understanding will contribute to better clinical management of the disease.

Original languageEnglish (US)
Pages (from-to)804-818
Number of pages15
JournalCancer Drug Resistance
Volume3
Issue number4
DOIs
StatePublished - 2020

Keywords

  • Androgen deprivation therapy
  • Castration-resistant prostate cancer
  • Epigenetics
  • MicroRNAs
  • Neuroendocrine differentiation
  • Oncomirs
  • Tumor suppressors

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology (medical)

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