Impact of novel miR-145-3p regulatory networks on survival in patients with castration-resistant prostate cancer

Br J Cancer. 2017 Jul 25;117(3):409-420. doi: 10.1038/bjc.2017.191. Epub 2017 Jun 22.


Background: Despite recent advancements, metastatic castration-resistant prostate cancer (CRPC) is not considered curative. Novel approaches for identification of therapeutic targets of CRPC are needed.

Methods: Next-generation sequencing revealed 945-1248 miRNAs from each lethal mCRPC sample. We constructed miRNA expression signatures of CRPC by comparing the expression of miRNAs between CRPC and normal prostate tissue or hormone-sensitive prostate cancer (HSPC). Genome-wide gene expression studies and in silico analyses were carried out to predict miRNA regulation and investigate the functional significance and clinical utility of the novel oncogenic pathways regulated by these miRNAs in prostate cancer (PCa).

Results: Based on the novel miRNA expression signature of CRPC, miR-145-5p and miR-145-3p were downregulated in CRPC. By focusing on miR-145-3p, which is a passenger strand and has not been well studied in previous reports, we showed that miR-145-3p targeted 4 key molecules, i.e., MELK, NCAPG, BUB1, and CDK1, in CPRC. These 4 genes significantly predicted survival in patients with PCa.

Conclusions: Small RNA sequencing for lethal CRPC and in silico analyses provided novel therapeutic targets for CRPC.

MeSH terms

  • Argonaute Proteins / genetics
  • CDC2 Protein Kinase
  • Cell Cycle Proteins / genetics
  • Cell Line, Tumor
  • Computer Simulation
  • Cyclin-Dependent Kinases / genetics
  • Disease-Free Survival
  • Down-Regulation
  • Gene Expression
  • Gene Expression Regulation, Neoplastic*
  • Genome-Wide Association Study
  • Humans
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Prostatic Neoplasms, Castration-Resistant / pathology*
  • Protein Serine-Threonine Kinases / genetics
  • RNA-Induced Silencing Complex
  • Sequence Analysis, RNA
  • Survival Rate


  • AGO2 protein, human
  • Argonaute Proteins
  • Cell Cycle Proteins
  • MIRN145 microRNA, human
  • MicroRNAs
  • NCAPG protein, human
  • RNA-Induced Silencing Complex
  • MELK protein, human
  • BUB1 protein, human
  • Protein Serine-Threonine Kinases
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Cyclin-Dependent Kinases