MicroRNA 15a, inversely correlated to PKCα, is a potential marker to differentiate between benign and malignant renal tumors in biopsy and urine samples.

Abstract

NF-κB signal transduction is a potential therapeutic target in many malignant tumors. We have recently shown, in malignant renal proximal tumor cells, that a transcription complex, consisting of NF-κB p65 and mitogen-activated protein kinase p38α, joined by protein kinase C (PKC) α, transmigrates into the nucleus. There, PKCα suppresses the nuclear release of primary microRNA (pri-miRNA) 15a. Induced by endothelin (ET)-1, a decrease in PKCα levels leads to increased miRNA 15a (miR-15A) expression. An identical system can be identified in renal carcinomas, in which, after nuclear transmigration, PKCα binds directly to pri-miRNA 15a in the nucleus. However, the pattern of PKC isoforms differs between malignant renal cell carcinoma (RCC) and benign oncocytoma. PKCα, a component of the transcription complex in tumors, is up-regulated in benign oncocytoma but down-regulated in RCC. Conversely, miRNA 15a is up-regulated in RCC and down-regulated in oncocytoma. A similar behavior is observed in chromophobe carcinoma, whereas differences are less pronounced in papillary RCC (type I): NF-κB target gene expression (ie, ET-1, ET-A and ET-B receptors, vascular cell adhesion molecule-1, IL-6, and fractalkine) is particularly high in malignant RCCs. Up-regulated miRNA 15a can be measured in urine from patients with RCC but is nearly undetectable in oncocytoma, other tumors, and urinary tract inflammation. Thus, the up-regulation of miRNA 15a may be an important marker to help identify malignant clear-cell RCCs in both biopsy and urine samples.

• Authors: Melanie von Brandenstein, Jency J Pandarakalam, Lukas Kroon, Heike Loeser, Jan Herden, Gabriele Braun, Katherina Wendland, Hans P Dienes, Udo Engelmann, Ullrich Engelmann, Jochen W U Fries
• Journal: The American journal of pathology (Am J Pathol) Vol. 180 Issue 5 Pg. 1787-97 (May 2012) ISSN: 1525-2191 [Electronic] United States
• PMID: 22429968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Isoenzymes
• MIRN15 microRNA, human
• MicroRNAs
• Protein Kinase C-alpha

Topics

• Adenoma, Oxyphilic (diagnosis, pathology)
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics, metabolism, urine)
• Biopsy
• Carcinoma, Renal Cell (diagnosis, pathology)
• Diagnosis, Differential
• Female
• Gene Expression Regulation, Enzymologic (physiology)
• Gene Expression Regulation, Neoplastic (physiology)
• Humans
• Isoenzymes (metabolism)
• Kidney Neoplasms (diagnosis, pathology)
• Male
• MicroRNAs (genetics, metabolism, urine)
• Middle Aged
• Protein Kinase C-alpha (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Signal Transduction (physiology)
• Up-Regulation (physiology)