The Prostate Cancer Cells Resistant to Docetaxel as in vitro Model for Discovering MicroRNAs Predictive of the Onset of Docetaxel Resistance

On the grounds that miRNAs present in the blood of prostate cancer (PCa) patients are released in the growth medium by PCa cells, it is conceivable that PCa cells resistant to docetaxel (DCT) (DCT(R)) will release miRNAs that may be found in PCa patients under DCT therapy if resistant PCa cells appear. We isolated DCT(R) clones respectively from 22Rv1 and DU-145 PCa cell lines and performed through next-generation sequencing (NGS) the miRNAs profiles of the released miRNAs. The analysis of the NGS data identified 105 and 1 miRNAs which were differentially released in the growth medium of the 22Rv1/DCT(R) and DU-145/DCT(R) clones, respectively. Using additional filters, we selected 12 and 1 miRNA more released by all 22Rv1/DCT(R) and DU-145/DCT(R) clones, respectively. Moreover, we showed that 6 of them were more represented in the growth medium of the DCT(R) cells than the ones of DCT-treated cells. We speculated that they have the pre-requisite to be tested as predictive biomarkers of the DCT resistance in PCa patients under DCT therapy. We propose the utilization of clones resistant to a given drug as in vitro model to identify the differentially released miRNAs, which in perspective could be tested as predictive biomarkers of drug resistance in tumor patients under therapy.

International journal of molecular sciences. 2017 Jul 13*** epublish ***

Lorenzo Bascetta, Arianna Oliviero, Romina D'Aurizio, Monica Evangelista, Alberto Mercatanti, Marco Pellegrini, Francesca Marrocolo, Sergio Bracarda, Milena Rizzo

Non-Coding RNA Laboratory, Institute of Clinical Physiology (IFC), National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy. ., Non-Coding RNA Laboratory, Institute of Clinical Physiology (IFC), National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy. ., Laboratory for Integrative System Medicine (LISM), Institute of Informatics and Telematics (IIT), National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy. ., Non-Coding RNA Laboratory, Institute of Clinical Physiology (IFC), National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy. ., Non-Coding RNA Laboratory, Institute of Clinical Physiology (IFC), National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy. ., Laboratory for Integrative System Medicine (LISM), Institute of Informatics and Telematics (IIT), National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy. ., Department of Oncology, San Donato Hospital, Azienda USL Toscana Sud-Est, via P. Nenni 20, 52100 Arezzo, Italy. ., Department of Oncology, San Donato Hospital, Azienda USL Toscana Sud-Est, via P. Nenni 20, 52100 Arezzo, Italy. ., Non-Coding RNA Laboratory, Institute of Clinical Physiology (IFC), National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy. .