Regulation of Neuroendocrine-like Differentiation in Prostate Cancer by Non-Coding RNAs

Abstract

Neuroendocrine prostate cancer (NEPC) represents a variant of prostate cancer that occurs in response to treatment resistance or, to a much lesser extent, de novo. Unravelling the molecular mechanisms behind transdifferentiation of cancer cells to neuroendocrine-like cancer cells is essential for development of new treatment opportunities. This review focuses on summarizing the role of small molecules, predominantly microRNAs, in this phenomenon. A published literature search was performed to identify microRNAs, which are reported and experimentally validated to modulate neuroendocrine markers and/or regulators and to affect the complex neuroendocrine phenotype. Next, available patients’ expression datasets were surveyed to identify deregulated microRNAs, and their effect on NEPC and prostate cancer progression is summarized. Finally, possibilities of miRNA detection and quantification in body fluids of prostate cancer patients and their possible use as liquid biopsy in prostate cancer monitoring are discussed. All the addressed clinical and experimental contexts point to an association of NEPC with upregulation of miR-375 and downregulation of miR-34a and miR-19b-3p. Together, this review provides an overview of different roles of non-coding RNAs in the emergence of neuroendocrine prostate cancer.

Clinical Significance of Extracellular Vesicles in Prostate and Renal Cancer

“…These usually include increased expression or dysregulation of miR-375, miR-34a, miR-19b-3p, and miR-30d-5p [60]. mi-R-375 in particular has been a focus of study for its diagnostic and prognostic potential in distinguishing benign and aggressive diseases as well as predicting treatment response [110,111]. Certain miRNAs, such as miR-301a, miR-34a, and miR-30 family members, were identified as AR regulators with binding sites in both UTR and coding regions of AR.…”