MicroRNA 15a, Inversely Correlated to PKC alpha, Is a Potential Marker to Differentiate between Benign and Malignant Renal Tumors in Biopsy and Urine Samples

作者：von Brandenstein Melanie; Pandarakalam Jency J; Kroon Lukas; Loeser Heike; Herden Jan; Braun Gabriele; Wendland Katherina; Dienes Hans P; Engelmann Ullrich; Fries Jochen W U^*

来源：American Journal Of Pathology, 2012, 180(5): 1787-1797.

DOI：10.1016/j.ajpath.2012.01.014

NF-kappa B 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-kappa B p65 and mitogen-activated protein kinase p38 alpha, joined by protein kinase C (PKC) alpha, transmigrates into the nucleus. There, PKC alpha suppresses the nuclear release of primary microRNA (pri-miRNA) 15a. Induced by endothelin (ET)-1, a decrease in PKC alpha levels leads to increased miRNA 15a (miR-15A) expression. An identical system can be identified in renal carcinomas, in which, after nuclear transmigration, PKC alpha 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. PKC alpha, 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-kappa B 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. (Am J Pathol 2012, 180:1787-1797; DOI: 10.1016/j.ajpath.2012.01.014)

• 出版日期2012-5