title: Exploring the role of miRNAs in renal cell carcinoma progression and metastasis through bioinformatic and experimental analyses.
abstract: Metastasis results in most of the cancer deaths in clear cell renal cell carcinoma (ccRCC). MicroRNAs (miRNAs) regulate many important cell functions and play important roles in tumor development, metastasis and progression. In our previous study, we identified a miRNA signature for metastatic RCC. In this study, we validated the top differentially expressed miRNAs on matched primary and metastatic ccRCC pairs by quantitative polymerase chain reaction. We performed bioinformatics analyses including target prediction and combinatorial analysis of previously reported miRNAs involved in tumour progression and metastasis. We also examined the co-expression of the miRNAs clusters and compared expression of intronic miRNAs and their host genes. We observed significant dysregulation between primary and metastatic tumours from the same patient. This indicates that, at least in part, the metastatic signature develops gradually during tumour progression. We identified metastasis-dysregulated miRNAs that can target a number of genes previously found to be involved in metastasis of kidney cancer as well as other malignancies. In addition, we found a negative correlation of expression of miR-126 and its target vascular endothelial growth factor (VEGF)-A. Cluster analysis showed that members of the same miRNA cluster follow the same expression pattern, suggesting the presence of a locus control regulation. We also observed a positive correlation of expression between intronic miRNAs and their host genes, thus revealing another potential control mechanism for miRNAs. Many of the significantly dysregulated miRNAs in metastatic ccRCC are highly conserved among species. Our analysis suggests that miRNAs are involved in ccRCC metastasis and may represent potential biomarkers.
authors.affiliation: Department of Laboratory Medicine and the Keenan Research Centre, Li Ka Shing Knowledge Institute of St Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada.
authors.forename: Heba W Z
authors.initials: HW
authors.lastname: Khella
authors.forename: Nicole M A
authors.initials: NM
authors.lastname: White
authors.forename: Hala
authors.initials: H
authors.lastname: Faragalla
authors.forename: Manal
authors.initials: M
authors.lastname: Gabril
authors.forename: Mina
authors.initials: M
authors.lastname: Boazak
authors.forename: David
authors.initials: D
authors.lastname: Dorian
authors.forename: Bishoy
authors.initials: B
authors.lastname: Khalil
authors.forename: Hany
authors.initials: H
authors.lastname: Antonios
authors.forename: Tian Tian
authors.initials: TT
authors.lastname: Bao
authors.forename: Maria D
authors.initials: MD
authors.lastname: Pasic
authors.forename: R John
authors.initials: RJ
authors.lastname: Honey
authors.forename: Robert
authors.initials: R
authors.lastname: Stewart
authors.forename: Kenneth T
authors.initials: KT
authors.lastname: Pace
authors.forename: Georg A
authors.initials: GA
authors.lastname: Bjarnason
authors.forename: Michael A S
authors.initials: MA
authors.lastname: Jewett
authors.forename: George M
authors.initials: GM
authors.lastname: Yousef
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000502:physiology*; D002292:Carcinoma, Renal Cell / Q000556:secondary*; D019295:Computational Biology; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A
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