Heishima Kazuki, Mori Takashi, Ichikawa Yukie, Sakai Hiroki, Kuranaga Yuki, Nakagawa Takayuki, Tanaka Yuiko, Okamura Yasuhiko, Masuzawa Mikio, Sugito Nobuhiko, Murakami Mami, Yamada Nami, Akao Yukihiro, Maruo Kohji
Department of Veterinary Clinical Oncology, Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, Japan.
United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan.
Int J Mol Sci. 2015 Oct 23;16(10):25377-91. doi: 10.3390/ijms161025377.
Malignant endothelial proliferative diseases including human angiosarcoma (AS) and canine hemangiosarcoma (HSA) are serious diseases with a grave prognosis. Establishing liquid biopsy-based biomarkers for screening has definite clinical utility; however, plasma miRNAs up- or down-regulated in these sarcomas have been unclear. For identifying possible diagnostic plasma miRNAs for these sarcomas, we investigated whether plasma miR-214 and miR-126, which miRNAs play important roles in angiogenesis and tumorigenesis, were elevated in malignant endothelial proliferative diseases. For this investigation, human angiosarcoma and canine hemangiosarcoma cell lines and clinical plasma samples of canine hemangiosarcoma were examined by performing miRNA qRT-PCR. We report here that human angiosarcoma and canine hemangiosarcoma cell lines over-secreted miR-214 and miR-126 via microvesicles; in addition, their levels in the plasma samples from canines with hemangiosarcoma were increased. Moreover, the surgical resection of primary tumors decreased the levels of plasma miR-214 and miR-126. Our findings suggest that these malignant endothelial proliferative diseases over-secreted miR-214 and miR-126, thus suggesting that these miRNAs have potential as diagnostic biomarkers for malignant endothelial proliferative diseases in canine and possible in human angiosarcoma.
恶性内皮细胞增殖性疾病，包括人类血管肉瘤（AS）和犬血管肉瘤（HSA），是预后严重的疾病。建立基于液体活检的生物标志物用于筛查具有明确的临床效用；然而，这些肉瘤中上调或下调的血浆miRNA尚不清楚。为了确定这些肉瘤可能的诊断性血浆miRNA，我们研究了在血管生成和肿瘤发生中起重要作用的血浆miR-214和miR-126在恶性内皮细胞增殖性疾病中是否升高。为了进行这项研究，通过进行miRNA qRT-PCR检测了人类血管肉瘤和犬血管肉瘤细胞系以及犬血管肉瘤的临床血浆样本。我们在此报告，人类血管肉瘤和犬血管肉瘤细胞系通过微泡过度分泌miR-214和miR-126；此外，它们在患有血管肉瘤的犬的血浆样本中的水平升高。此外，原发性肿瘤的手术切除降低了血浆miR-214和miR-126的水平。我们的研究结果表明，这些恶性内皮细胞增殖性疾病过度分泌miR-214和miR-126，因此表明这些miRNA有可能作为犬恶性内皮细胞增殖性疾病以及可能的人类血管肉瘤的诊断生物标志物。
