miRNA profiling in metastatic renal cell carcinoma reveals a tumour-suppressor effect for miR-215.
BACKGROUND
Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Metastatic RCC is difficult to treat. The 5-year survival rate for metastatic RCC is ≤10%. Recently, microRNAs (miRNAs) have been shown to have a role in cancer metastasis and potential as prognostic biomarkers in cancer.


METHODS
We performed a miRNA microarray to identify a miRNA signature characteristic of metastatic compared with primary RCCs. We validated our results by quantitative real-time PCR. We performed experimental and bioinformatic analyses to explore the involvement of miR-215 in RCC progression and metastasis.


RESULTS
We identified 65 miRNAs that were significantly altered in metastatic compared with primary RCCs. We validated our results by examining the expression of miR-10b, miR-126, miR-196a, miR-204 and miR-215, in two independent cohorts of patients. We showed that overexpression of miR-215 decreased cellular migration and invasion in an RCC cell line model. In addition, through gene expression profiling, we identified direct and indirect targets of miR-215 that can contribute to tumour metastasis.


CONCLUSIONS
Our analysis showed that miRNAs are altered in metastatic RCCs and can contribute to kidney cancer metastasis through different biological processes. Dysregulated miRNAs represent potential prognostic biomarkers and may have therapeutic applications in kidney cancer.
Department of Laboratory Medicine and Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada.
N M A
NM
White
H W Z
HW
Khella
J
J
Grigull
S
S
Adzovic
Y M
YM
Youssef
R J
RJ
Honey
R
R
Stewart
K T
KT
Pace
G A
GA
Bjarnason
M A S
MA
Jewett
A J
AJ
Evans
M
M
Gabril
G M
GM
Yousef
D014408:Biomarkers, Tumor / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005820:Genetic Testing / Q000379:methods; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis / Q000379:methods; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012097:Repressor Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015996:Survival Rate; D000074165:Zinc Finger E-box Binding Homeobox 2
D014408:Biomarkers, Tumor; C108381:GEMIN2 protein, human; D018398:Homeodomain Proteins; C553667:MIRN215 microRNA, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2