title: 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.affiliation: Institute of Pathology, University Hospital, Cologne, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: von Brandenstein
authors.forename: Jency J
authors.initials: JJ
authors.lastname: Pandarakalam
authors.forename: Lukas
authors.initials: L
authors.lastname: Kroon
authors.forename: Heike
authors.initials: H
authors.lastname: Loeser
authors.forename: Jan
authors.initials: J
authors.lastname: Herden
authors.forename: Gabriele
authors.initials: G
authors.lastname: Braun
authors.forename: Katherina
authors.initials: K
authors.lastname: Wendland
authors.forename: Hans P
authors.initials: HP
authors.lastname: Dienes
authors.forename: Udo
authors.initials: U
authors.lastname: Engelmann
authors.forename: Ullrich
authors.initials: U
authors.lastname: Engelmann
authors.forename: Jochen W U
authors.initials: JW
authors.lastname: Fries
mesh_terms: D018249:Adenoma, Oxyphilic / Q000175:diagnosis* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D001706:Biopsy; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D008875:Middle Aged; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; C505361:MIRN15 microRNA, human; D035683:MicroRNAs; D051571:Protein Kinase C-alpha