Abstract
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.
Highlights
Malignant endothelial proliferative diseases such as human angiosarcoma (AS) and canine hemangiosarcoma (HSA) are both serious diseases
HSA, which is a spontaneous model of AS
Establishing a miRNA-based screening test has definite clinical significance; circulating miRNAs, which are up- or down-regulated in HSA and AS, has been unclear
Summary
Malignant endothelial proliferative diseases such as human angiosarcoma (AS) and canine hemangiosarcoma (HSA) are both serious diseases. These miRNAs carried in MVs are protected from RNase and are stable in the bloodstream Their secretion profiles in plasma reflect biological changes such as tumorigenesis, progression, and metastasis [5]; plasma miRNAs have potential to be stable, accurate, and non-invasive blood-based biomarkers for screening for malignant neoplasms. MiR-214 and miR-126 are miRNAs playing important roles in angiogenesis and tumorigenesis intracellularly and are released into the surrounding biofluid such as blood and serve certain functions [6,7]; these two miRNAs are candidates to be up-regulated in the plasma of malignant endothelial proliferative disease such as HSA and AS. Plasma samples obtained from the canines with HSA showed high levels of miR-214 and miR-126, suggesting that these miRNAs have potential to be biomarkers for HSA and might be applicable for diagnosing AS
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