Deregulated microRNAs Involved in Prostate Cancer Aggressiveness and Treatment Resistance Mechanisms

Abstract

Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer deaths among American men. Complex genetic and epigenetic mechanisms are involved in the development and progression of PCa. MicroRNAs (miRNAs) are short noncoding RNAs that regulate protein expression at the post-transcriptional level by targeting mRNAs for degradation or inhibiting protein translation. In the past two decades, the field of miRNA research has rapidly expanded, and emerging evidence has revealed miRNA dysfunction to be an important epigenetic mechanism underlying a wide range of diseases, including cancers. This review article focuses on understanding the functional roles and molecular mechanisms of deregulated miRNAs in PCa aggressiveness and drug resistance based on the existing literature. Specifically, the miRNAs differentially expressed (upregulated or downregulated) in PCa vs. normal tissues, advanced vs. low-grade PCa, and treatment-responsive vs. non-responsive PCa are discussed. In particular, the oncogenic and tumor-suppressive miRNAs involved in the regulation of (1) the synthesis of the androgen receptor (AR) and its AR-V7 splice variant, (2) PTEN expression and PTEN-mediated signaling, (3) RNA splicing mechanisms, (4) chemo- and hormone-therapy resistance, and (5) racial disparities in PCa are discussed and summarized. We further provide an overview of the current advances and challenges of miRNA-based biomarkers and therapeutics in clinical practice for PCa diagnosis/prognosis and treatment.

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“…Epigenetics is also involved in regulating cell differentiation and development 48 . Differential expression of microRNAs is a critical epigenetic mechanism involved in the development and progression of human PC 49 . We previously demonstrated that miR-145, miR-148, and miR-185 were differentially expressed among patients with PC, PL and BPH 26 .…”

Unlocking Precision Medicine: Liquid Biopsy Advancements in Renal Cancer Detection and Monitoring

“…The complete or partial pairing between miRNA and target mRNA, respectively, leads to the degradation or inhibition of protein translation genes. With this mechanism of action, miRNAs are involved in cell development, viral infection, immune response, angiogenesis, and the progression of many pathologies including breast, lung, colorectal, and prostate cancer [12][13][14][15].…”

Regulation of Molecular Biomarkers Associated with the Progression of Prostate Cancer

“…The genetic mechanism(s) that results in the loss of function of PTEN during the development of CRPC are not well understood. However, several miRNAs are involved in downregulating PTEN expression in PCa, suggesting that the deregulation of miRNA expression mediates the loss of PTEN function during PCa progression [60].…”