RNA Sequencing of Collecting Duct Renal Cell Carcinoma Suggests an Interaction between miRNA and Target Genes and a Predominance of Deregulated Solute Carrier Genes

• Main Authors: Sven Wach, Helge Taubert, Katrin Weigelt, Nora Hase, Marcel Köhn, Danny Misiak, Stefan Hüttelmaier, Christine G. Stöhr, Andreas Kahlmeyer, Florian Haller, Julio Vera, Arndt Hartmann, Bernd Wullich, Xin Lai
• Format: Article
• Language: English
• Published: MDPI AG 2019-12-01
• Series: Cancers
• Subjects: collecting duct carcinoma; rna sequencing; solute carrier proteins
• Online Access: https://www.mdpi.com/2072-6694/12/1/64

Collecting duct carcinoma (CDC) is a rare renal cell carcinoma subtype with a very poor prognosis. There have been only a few studies on gene expression analysis in CDCs. We compared the gene expression profiles of two CDC cases with those of eight normal tissues of renal cell carcinoma patients. At a threshold of |log2fold-change| &#8805;1, 3349 genes were upregulated and 1947 genes were downregulated in CDCs compared to the normal samples. Pathway analysis of the deregulated genes revealed that cancer pathways and cell cycle pathways were most prominent in CDCs. The most upregulated gene was <i>keratin 17</i>, and the most downregulated gene was <i>cubilin</i>. Among the most downregulated genes were four solute carrier genes (<i>SLC3A1</i>, <i>SLC9A3</i>, <i>SLC26A7</i>, and <i>SLC47A1</i>). The strongest negative correlations between miRNAs and mRNAs were found between the downregulated miR-374b-5p and its upregulated target genes <i>HIST1H3B</i>, <i>HK2</i>, and <i>SLC7A11</i> and between upregulated miR-26b-5p and its downregulated target genes <i>PPARGC1A</i>, <i>ALDH6A1</i>, and <i>MARC2</i>. An upregulation of HK2 and a downregulation of PPARGC1A, ALDH6A1, and MARC2 were observed at the protein level. Survival analysis of the cancer genome atlas (TCGA) dataset showed for the first time that low gene expression of <i>MARC2</i>, <i>cubilin</i>, and <i>SLC47A1</i> and high gene expression of <i>KRT17</i> are associated with poor overall survival in clear cell renal cell carcinoma patients. Altogether, we identified dysregulated protein-coding genes, potential miRNA-target interactions, and prognostic markers that could be associated with CDC.