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Tumor Biology

, Volume 35, Issue 7, pp 7105–7113 | Cite as

Influence of peripheral whole-blood microRNA-7 and microRNA-221 high expression levels on the acquisition of castration-resistant prostate cancer: evidences from in vitro and in vivo studies

  • Juliana I. Santos
  • Ana L. Teixeira
  • Francisca Dias
  • Joaquina Maurício
  • Francisco Lobo
  • António Morais
  • Rui Medeiros
Research Article

Abstract

Prostate cancer (PC) is the more frequently diagnosed neoplasia in men in developed countries. The evolution of PC to castration-resistant prostate cancer (CRPC) represents real problems of clinical management, in consequence to the limited therapeutic options. MicroRNAs (miRNAs) are small noncoding RNAs that play an important role in gene expression and function regulation. The increased evidence that miRNAs are involved in cancer development and progression has made them potential biomarkers for cancer diagnosis, prognosis, and aggressiveness. Our purpose was to identify a miRNA expression profile associated with the development of CRPC. We firstly observed a miRNA expression profile differentially expressed between the castration-resistant (CR) PC3 cell line and the hormone-sensitive LnCaP cell line, where miR-7, miR-221, and miR-222 were upregulated in PC3 (11.3-fold increase, P = 0.012; 11.3-fold increase, P = 0.002; 8.6-fold increase, P = 0.002, respectively). We also observed that the trend of miR-1233 expression levels was higher in PC3 (3.7-fold increase, P = 0.057). These miRNAs differentially expressed in vitro were studied in a peripheral whole-blood samples from PC patients. We observed that patients presenting an early CR acquisition (≤20 months) had higher expression levels of miR-7 and miR-221 (P = 0.034 and P = 0.036, respectively). Furthermore, we found that patients diagnosed with high-Gleason score tumors and presenting simultaneous higher miR-7 expression levels have a significant reduce time to CR compared with patients who present lower miR-7 expression levels (11 vs. 51 months, log-rank test P = 0.004). We also found that patients diagnosed with high-Gleason score tumors and higher expression levels of miR-221 have an early CRPC compared to patients with lower miR-221 expression levels (10 vs. 46 months, log-rank test P = 0.012). We observed a significantly lower overall survival in patients with higher peripheral whole-blood expression levels of miR-7 (28 vs. 116 months, log-rank test P = 0.001). Our results suggest that miR-7 and miR-221 peripheral whole-blood expression levels can be potential predictive biomarkers of CRPC development.

Keywords

Prostate cancer CRPC development Peripheral whole-blood microRNAs miR-7 miR-221 

Abbreviations

PC

Prostate cancer

CRPC

Castration-resistant prostate cancer

ADT

Androgen deprivation therapy

miRNAs

MicroRNAs

mRNAs

Messenger RNAs

EGFR

Epidermal growth factor receptor

MMP

Matrix metalloproteinase

mTOR

Mammalian target of rapamycin

CR

Castration-resistant

EMT

Epithelial-mesenchymal transition

TIMP3

Metalloproteinase inhibitor 3

RECK

Reversion-inducing-cysteine-rich protein with kazal motifs

RCC

Renal cell carcinoma

HIF-1α

Hypoxia-inducible factor 1-alpha

Notes

Acknowledgments

We would like to thank the Liga Portuguesa Contra o Cancro—Centro Regional do Norte (Portuguese League Against Cancer) and FCT—Fundação para a Ciência e Tecnologia. ALT is a doctoral degree grant holder from FCT (SFRH/BD/47381/2008).

Conflicts of interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Juliana I. Santos
    • 1
    • 2
  • Ana L. Teixeira
    • 1
    • 2
  • Francisca Dias
    • 1
    • 2
  • Joaquina Maurício
    • 1
  • Francisco Lobo
    • 1
  • António Morais
    • 1
  • Rui Medeiros
    • 1
    • 2
    • 3
    • 4
  1. 1.Molecular Oncology GroupPortuguese Institute of Oncology of PortoPorto 4200-072Portugal
  2. 2.ICBAS, Abel Salazar Institute for the Biomedical SciencesUniversity of PortoPorto 4050-313Portugal
  3. 3.Research DepartmentLPCC-Portuguese League Against Cancer (NRNorte)Porto 4200-177Portugal
  4. 4.CEBIMEDFaculty of Health Sciences of Fernando Pessoa UniversityPorto 4200-150Portugal

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