Grimes Janet A, Prasad Nripesh, Levy Shawn, Cattley Russell, Lindley Stephanie, Boothe Harry W, Henderson Ralph A, Smith Bruce F
Department of Clinical Sciences, Auburn University College of Veterinary Medicine, Auburn University, Auburn, AL, USA.
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, 2200 College Station Road, Athens, GA, 30602, USA.
BMC Vet Res. 2016 Dec 3;12(1):272. doi: 10.1186/s12917-016-0903-5.
Splenic masses are common in older dogs; yet diagnosis preceding splenectomy and histopathology remains elusive. MicroRNAs (miRNAs) are short, non-coding RNAs that play a role in post-transcriptional regulation, and differential expression of miRNAs between normal and tumor tissue has been used to diagnose neoplastic diseases. The objective of this study was to determine differential expression of miRNAs by use of RNA-sequencing in canine spleens that were histologically confirmed as hemangiosarcoma, nodular hyperplasia, or normal.
Twenty-two miRNAs were found to be differentially expressed in hemangiosarcoma samples (4 between hemangiosarcoma and both nodular hyperplasia and normal spleen and 18 between hemangiosarcoma and normal spleen only). In particular, mir-26a, mir-126, mir-139, mir-140, mir-150, mir-203, mir-424, mir-503, mir-505, mir-542, mir-30e, mir-33b, mir-365, mir-758, mir-22, and mir-452 are of interest in the pathogenesis of hemangiosarcoma.
Findings of this study confirm the hypothesis that miRNA expression profiles are different between canine splenic hemangiosarcoma, nodular hyperplasia, and normal spleens. A large portion of the differentially expressed miRNAs have roles in angiogenesis, with an additional group of miRNAs being dysregulated in vascular disease processes. Two other miRNAs have been implicated in cancer pathways such as PTEN and cell cycle checkpoints. The finding of multiple miRNAs with roles in angiogenesis and vascular disease is important, as hemangiosarcoma is a tumor of endothelial cells, which are driven by angiogenic stimuli. This study shows that miRNA dysregulation is a potential player in the pathogenesis of canine splenic hemangiosarcoma.
脾脏肿块在老年犬中很常见；然而，在脾切除和组织病理学检查之前进行诊断仍然很困难。微小RNA（miRNA）是短的非编码RNA，在转录后调控中发挥作用，正常组织和肿瘤组织之间miRNA的差异表达已被用于诊断肿瘤性疾病。本研究的目的是通过RNA测序确定组织学确诊为血管肉瘤、结节性增生或正常的犬脾脏中miRNA的差异表达。
发现22种miRNA在血管肉瘤样本中差异表达（4种在血管肉瘤与结节性增生和正常脾脏中均有差异，18种仅在血管肉瘤与正常脾脏中存在差异）。特别是，mir-26a、mir-126、mir-139、mir-140、mir-150、mir-203、mir-424、mir-503、mir-505、mir-542、mir-30e、mir-33b、mir-365、mir-758、mir-22和mir-452在血管肉瘤的发病机制中具有重要意义。
本研究结果证实了以下假设，即犬脾脏血管肉瘤、结节性增生和正常脾脏之间的miRNA表达谱不同。大部分差异表达的miRNA在血管生成中发挥作用，另有一组miRNA在血管疾病过程中失调。另外两种miRNA与癌症途径如PTEN和细胞周期检查点有关。发现多种在血管生成和血管疾病中起作用的miRNA很重要，因为血管肉瘤是一种内皮细胞肿瘤，由血管生成刺激驱动。本研究表明，miRNA失调是犬脾脏血管肉瘤发病机制中的一个潜在因素。
