Comprehensive gene expression analysis of canine invasive urothelial bladder carcinoma by RNA-Seq

Abstract

BackgroundInvasive urothelial carcinoma (iUC) is a major cause of death in humans, and approximately 165,000 individuals succumb to this cancer annually worldwide. Comparative oncology using relevant animal models is necessary to improve our understanding of progression, diagnosis, and treatment of iUC. Companion canines are a preferred animal model of iUC due to spontaneous tumor development and similarity to human disease in terms of histopathology, metastatic behavior, and treatment response. However, the comprehensive molecular characterization of canine iUC is not well documented. In this study, we performed transcriptome analysis of tissue samples from canine iUC and normal bladders using an RNA sequencing (RNA-Seq) approach to identify key molecular pathways in canine iUC.MethodsTotal RNA was extracted from bladder tissues of 11 dogs with iUC and five healthy dogs, and RNA-Seq was conducted. Ingenuity Pathway Analysis (IPA) was used to assign differentially expressed genes to known upstream regulators and functional networks.ResultsDifferential gene expression analysis of the RNA-Seq data revealed 2531 differentially expressed genes, comprising 1007 upregulated and 1524 downregulated genes, in canine iUC. IPA revealed that the most activated upstream regulator was PTGER2 (encoding the prostaglandin E2 receptor EP2), which is consistent with the therapeutic efficiency of cyclooxygenase inhibitors in canine iUC. Similar to human iUC, canine iUC exhibited upregulated ERBB2 and downregulated TP53 pathways. Biological functions associated with cancer, cell proliferation, and leukocyte migration were predicted to be activated, while muscle functions were predicted to be inhibited, indicating muscle-invasive tumor property.ConclusionsOur data confirmed similarities in gene expression patterns between canine and human iUC and identified potential therapeutic targets (PTGER2, ERBB2, CCND1, Vegf, and EGFR), suggesting the value of naturally occurring canine iUC as a relevant animal model for human iUC.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4409-3) contains supplementary material, which is available to authorized users.

LncRNA LINP1 regulates acute myeloid leukemia progression via HNF4α/AMPK/WNT5A signaling pathway

“…RNA‐Seq was performed as described previously . Briefly, total RNA was extracted from KG‐1 cells transfected with sh‐LINP1 and sh‐NC using the RNeasy Mini Kit (Qiagen, Valencia, CA).…”

“…RNA-Seq was performed as described previously. 11 Briefly, total RNA was extracted from KG-1 cells transfected with sh-LINP1 and sh-NC using the RNeasy Mini Kit (Qiagen, Valencia, CA). Sequencing libraries were constructed using the TruSeq Stranded mRNA Library PrepKit for NeoPrep (Illumina, USA).…”

A comparative meta andin silicoanalysis of differentially expressed genes and proteins in canine and human bladder cancer

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Anti‐tumour effect of lapatinib in canine transitional cell carcinoma cell lines

“…Our previous study, using RNA sequencing for urinary bladder (UB) tissues in dogs with TCC and healthy dogs, showed that human epidermal growth factor 2 (HER2) was the most activated upstream regulator related with carcinogenesis in canine TCC . The HER2 protein is a 185‐kD transmembrane glycoprotein part of the HER family of tyrosine kinase receptors, which include HER1 (also known as epidermal growth factor receptor [EGFR]), HER2, HER3, and HER4.…”

“…3 Thus, a novel therapeutic option with increased survival time is currently needed for treatment of canine TCC.Our previous study, using RNA sequencing for urinary bladder (UB) tissues in dogs with TCC and healthy dogs, showed that human epidermal growth factor 2 (HER2) was the most activated upstream regulator related with carcinogenesis in canine TCC. 4 The HER2 protein is a 185-kD transmembrane glycoprotein part of the HER family of tyrosine kinase receptors, which include HER1 (also known as epidermal growth factor receptor [EGFR]), HER2, HER3, and HER4. In normal circumstances, HER2 is involved in proliferation, differentiation, angiogenesis, and migration through two principal signalling pathways: the mitogen-activated protein kinase/extracellular-…”