Low Expression of miR-126 Is a Prognostic Marker for Metastatic Clear Cell Renal Cell Carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with unpredictable behavior. Clinical parameters are not always accurate for predicting prognosis. miR-126 is differentially expressed in many cancers, including RCC, and is down-regulated in metastatic versus primary ccRCC. We assessed the prognostic significance of miR-126 in 264 primary ccRCCs. We also compared its expression in normal kidney, primary and metastatic ccRCC, and RCC subtypes. We validated our results on an independent set of 481 ccRCCs. miR-126 was down-regulated in metastatic versus primary tumors and in tumors of higher stage (P = 0.005) or higher grade (P = 0.002). miR-126 up-regulation was associated with significantly prolonged disease-free survival (P < 0.001) and overall survival (P = 0.015). For larger tumors (>4 cm), patients with higher miR-126 expression had significantly longer survival. Restoration of miR-126 expression decreased cellular migration and proliferation in RCC cell lines. The ccRCCs exhibited the highest miR-126 expression, and papillary RCCs exhibited the lowest expression. We identified a number of miR-126 targets and pathways that are involved in carcinogenesis, including the apoptosis signaling pathway. miR-126 is a promising prognostic marker in ccRCC that can distinguish between clear cell and papillary subtypes. In addition, miR-126 has potential therapeutic applications.

miR-10b is a prognostic marker in clear cell renal cell carcinoma

“…A total of 262 cases of primary and metastatic ccRCC (250 primary and 12 metastatic) were analysed, as detailed in our previous publications 27. Formalin-fixed paraffin-embedded tissues were collected from St Michael's Hospital, and University Health Network, Toronto, Canada.…”

“…We performed target prediction analysis using TargetScanHuman 6.2 (http://www.targetscan.org/) and miRecords (http://c1.accurascience.com/miRecords/) software, as in our previous publications 27. We further filtered the predicted gene targets list through literature search and pathway analysis using DIANA-mirPath (http://diana.imis.athena-innovation.gr/DianaTools/index.php?r=mirpath/index) and the Gene Functional Classification tool from DAVID Bioinformatics database (http://david.abcc.ncifcrf.gov/gene2gene.jsp).…”

Pseudohypoxia induced by miR-126 deactivation promotes migration and therapeutic resistance in renal cell carcinoma

“…miRNA expression changes have been demonstrated in many types of cancer, suggesting their potential values in cancer diagnosis, prognosis and treatment. Up- or down-regulated miRNA expression levels in RCC have been described and reviewed in recent literature [8–10]. Certain key molecules for ccRCC, such as HIFα, VEGF and mTOR, are possible targets of these dysregulated miRNAs.…”

microRNAs Distinctively Regulate Vascular Smooth Muscle and Endothelial Cells: Functional Implications in Angiogenesis, Atherosclerosis, and In-Stent Restenosis

“…A significant increase in circulating miR-126 has been detected in patients with acute myocardial infarction and angina whereas miR-126 downregulation has been reported in plasma from patients with diabetes, heart failure, or cancer [14]. Hence, circulating miR-126 can be modulated by diverse stimuli inducing dissimilar cellular fates in different cell types [60, 85, 93–97]. Most recently, Italian researchers demonstrated that circulating miR-126-3p (see Chap.…”