Exploring the Role of miRNAs in Renal Cell Carcinoma Progression and Metastasis through Bioinformatic and Experimental Analyses
Heba WZ Khella, Nicole MA White, Hala Faragalla, Manal Gabril, Mina Boazak, David Dorian, Bishoy Khalil, Tian Tian Bao, Maria D Pasic, R John Honey, Robert Stewart, Kenneth T Pace, Georg A Bjarnason, Michael Jewett, George M Yousef. Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada; London Health Sciences Centre, London, ON, Canada; St. Michael's Hospital, Toronto, ON, Canada; Sunnybrook Odette Cancer Center, Toronto, ON, Canada
Background: Metastasis results in most of the cancer deaths in RCC. miRNAs regulate many important cell functions and play an important roles in tumor development, metastasis and progression. In our previous study, we identified, through microarray analysis, a miRNA signature for metastatic RCC.
Design: We validated the top differentially expressed miRNAs on matched primary and metastatic ccRCC pairs by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). We performed bioinformatics analyses including target prediction and combinatorial analysis of previously reported miRNAs involved in tumour progression and metastasis. In addition, we examined the co-expression of the miRNAs clusters and compared the expression patterns of intronic miRNAs and their host genes.
Results: 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 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.
Conclusions: Our analysis suggests that miRNAs are involved in ccRCC metastasis and may represent potential biomarkers for kidney cancer metastasis.
Category: Genitourinary (including renal tumors)
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 97, Wednesday Morning