miR-34a is an intracellular and exosomal predictive biomarker for response to docetaxel with clinical relevance to prostate cancer progression.

File Type:
PDFItem Type:
Journal ArticleDate:
2014Author:
Access:
openAccessCitation:
Corcoran C, Rani S, O'Driscoll L, miR-34a is an intracellular and exosomal predictive biomarker for response to docetaxel with clinical relevance to prostate cancer progression., The Prostate, 74, 13, 2014, 1320 - 1334Download Item:
Abstract:
BACKGROUND
Docetaxel-resistance limits successful treatment of castration resistant prostate cancer. We previously demonstrated that extracellular vesicles (exosomes) may play a role in regulating docetaxel resistance. Here, we investigated intracellular and extracellular (exosomal) miRNAs related to docetaxel resistance.
METHODS
Following global miRNA profiling of cell line models of docetaxel-resistance and their corresponding exosomes, we investigated the clinical relevance of four selected miRNAs (miR-598, miR-34a, miR-146a, miR-148a) in four publically available clinical cohorts representing both primary and advanced disease in tissue and urine specimens. One of these miRNAs, miR-34a was selected for functional evaluation by miRNA inhibition and over-expression in vitro. We further assessed the panel of miRNAs for their combined clinical relevance as a biomarker signature by examining their common predicted targets.
RESULTS
A strong correlation was found between the detection of miRNAs in exosomes and their corresponding cells of origin. Of the miRNAs chosen for further validation and clinical assessment, decreased miR-34a levels showed substantial clinical relevance and so was chosen for further analysis. Manipulating miR-34a in prostate cancer cells confirms that this miRNA regulates BCL-2 and may, in part, regulate response to docetaxel. When combined, these miRNAs are predicted to regulate a range of common mRNA targets, two of which (e.g., SNCA, SCL7A5) demonstrate a strong relationship with prostate cancer progression and poor prognosis.
CONCLUSIONS
This study supports the extracellular environment as an important source of minimally invasive predictive biomarkers representing their cellular origin. Using miR-34a as example, we showed that biomarkers identified in this manner may also hold functional relevance.
Author's Homepage:
http://people.tcd.ie/lodriscDescription:
PUBLISHED
Author: O'Driscoll, Lorraine
Type of material:
Journal ArticleSeries/Report no:
The Prostate74
13
Availability:
Full text availableSubject:
docetaxel-resistance, prostate cancer, exosomes, microRNA, biomarkers, miR-34a, BCL-2Subject (TCD):
CancerDOI:
10.1002/pros.22848.ISSN:
0270-4137Metadata
Show full item recordThe following license files are associated with this item: