Unknown

Dataset Information

0

Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma.


ABSTRACT: To identify tissue microRNAs predictive of sunitinib activity in patients with metastatic renal-cell-carcinoma (MRCC) and to evaluate in vitro their mechanism of action in sunitinib resistance.We screened 673 microRNAs using TaqMan Low-density-Arrays (TLDAs) in tumors from MRCC patients with extreme phenotypes of marked efficacy and resistance to sunitinib, selected from an identification cohort (n = 41). The most relevant differentially expressed microRNAs were selected using bioinformatics-based target prediction analysis and quantified by qRT-PCR in tumors from patients presenting similar phenotypes selected from an independent cohort (n = 101). In vitro experiments were conducted to study the role of miR-942 in sunitinib resistance.TLDAs identified 64 microRNAs differentially expressed in the identification cohort. Seven candidates were quantified by qRT-PCR in the independent series. MiR-942 was the most accurate predictor of sunitinib efficacy (p = 0.0074). High expression of miR-942, miR-628-5p, miR-133a, and miR-484 was significantly associated with decreased time to progression and overall survival. These microRNAs were also overexpressed in the sunitinib resistant cell line Caki-2 in comparison with the sensitive cell line. MiR-942 overexpression in Caki-2 up-regulates MMP-9 and VEGF secretion which, in turn, promote HBMEC endothelial migration and sunitinib resistance.We identified differentially expressed microRNAs in MRCC patients presenting marked sensitivity or resistance to sunitinib. MiR-942 was the best predictor of efficacy. We describe a novel paracrine mechanism through which high miR-942 levels in MRCC cells up-regulates MMP-9 and VEGF secretion to enhance endothelial migration and sunitinib resistance. Our results support further validation of these miRNA in clinical confirmatory studies.

SUBMITTER: Prior C 

PROVIDER: S-EPMC3901669 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

altmetric image

Publications


<h4>Purpose</h4>To identify tissue microRNAs predictive of sunitinib activity in patients with metastatic renal-cell-carcinoma (MRCC) and to evaluate in vitro their mechanism of action in sunitinib resistance.<h4>Methods</h4>We screened 673 microRNAs using TaqMan Low-density-Arrays (TLDAs) in tumors from MRCC patients with extreme phenotypes of marked efficacy and resistance to sunitinib, selected from an identification cohort (n = 41). The most relevant differentially expressed microRNAs were s  ...[more]

Similar Datasets

2014-09-30 | E-GEOD-37766 | biostudies-arrayexpress
2014-09-30 | GSE37766 | GEO
2018-02-08 | E-MTAB-6296 | biostudies-arrayexpress
| S-EPMC5580299 | biostudies-literature
| S-EPMC5259767 | biostudies-literature
| S-EPMC3785463 | biostudies-other
| S-EPMC5117167 | biostudies-literature
| S-EPMC3950861 | biostudies-literature
| S-EPMC5516884 | biostudies-literature
| S-EPMC4705883 | biostudies-other