MicroRNA-214 and MicroRNA-126 Are Potential Biomarkers for Malignant Endothelial Proliferative Diseases

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.

A comparison of microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs

“…Both the study reported here and the previously published works had relatively small sample numbers, and evaluation of a larger sample size may help to clarify these confounding results [84, 85]. Despite the lack of agreement in the findings of mir-214, the results reported here agree with the findings of mir-126 reported by the previous group, in which they found overexpression of mir-126 in plasma samples of canine patients with hemangiosarcoma [85]. These previous studies only evaluated mir-214 and mir-126 expression and did not evaluate for other miRNAs, but the finding of mir-126 overexpression, similar to the findings of the current study, is noteworthy.…”

“…Later work by the same group found overexpression of mir-214 in the media of canine hemangiosarcoma and human angiosarcoma cell lines, which contradicted their previous findings of underexpression within the cells themselves [85]. They also found increased expression of mir-214 in the plasma of canine patients with hemangiosarcoma, which decreased after tumor removal [85]. The explanation for the contradictory findings in these studies was that intracellular and extracellular concentrations of miRNAs can be different and because miRNAs can have a multitude of downstream targets, they may act differently depending on their location and the disease state.…”

“…One reason for this may have been the methods used to evaluate for differential expression of miRNA. In the study reported here, RNA-sequencing was used to determine differentially expressed miRNAs, compared to the previously reported studies which used qRT-PCR to evaluate for miRNAs [84, 85]. Both the study reported here and the previously published works had relatively small sample numbers, and evaluation of a larger sample size may help to clarify these confounding results [84, 85].…”

“…This miRNA was found to act as a tumor suppressor by promoting apoptosis, and was downregulated in their samples [84]. Later work by the same group found overexpression of mir-214 in the media of canine hemangiosarcoma and human angiosarcoma cell lines, which contradicted their previous findings of underexpression within the cells themselves [85]. They also found increased expression of mir-214 in the plasma of canine patients with hemangiosarcoma, which decreased after tumor removal [85].…”

“…In the study reported here, RNA-sequencing was used to determine differentially expressed miRNAs, compared to the previously reported studies which used qRT-PCR to evaluate for miRNAs [84, 85]. Both the study reported here and the previously published works had relatively small sample numbers, and evaluation of a larger sample size may help to clarify these confounding results [84, 85]. Despite the lack of agreement in the findings of mir-214, the results reported here agree with the findings of mir-126 reported by the previous group, in which they found overexpression of mir-126 in plasma samples of canine patients with hemangiosarcoma [85].…”