Gathering Novel Circulating Exosomal microRNA in Osteosarcoma Cell Lines and Possible Implications for the Disease

Abstract

One of the goals of personalized medicine is to understand and treat diseases with greater precision through the molecular profile of the patient. This profiling is becoming a powerful tool for the discovery of novel biomarkers that can guide physicians in assessing, in advance, the disease stage, and monitoring disease progression. Circulating miRNAs and exosomal miRNAs, a group of small non-coding RNAs, are considered the gold standard diagnostic biomarkers for human diseases. We have previously demonstrated that osteosarcoma-derived exosomes are able to influence crucial mechanisms inside tumor niches, inducing osteoclast differentiation, and sustaining bone resorption activity. Here we discovered, through Next-Generation Sequencing (NGS), eight novel microRNAs in three different osteosarcoma cell lines, and assessed the selective packaging into the exosomes released. We then investigated, as proof-of-principle, the presence of the novel microRNAs in osteosarcoma patient samples, and found that 5 of the 8 novel microRNAs were more present in circulating exosomes of osteosarcoma patients compared with the controls. These results raise a question: Could the 8 novel microRNAs play a role for osteosarcoma pathogenesis? Although still premature, the results are encouraging, and further studies with a validation in a larger cohort are needed.

Tumor suppressing role of serum-derived exosomal microRNA-15a in osteosarcoma cells through the GATA binding protein 2/murine double minute 2 axis and the p53 signaling pathway

“…A recent study by Wang et al reported that exosomal miR-21 expression in serum and plasma from patients with OS differed from that in normal patients, and that exosomal miR-21 plays important roles in OS tumorigenesis [34]. In addition, a review by Cuscino et al revealed that eight exosomal miRNAs may be implicated in OS progression [35].…”

Exosomes as Efficient Nanocarriers in Osteosarcoma: Biological Functions and Potential Clinical Applications

“…The study demonstrated that serum exosome derived miR-675 expression may serve as a new biomarker for osteosarcoma metastasis ( Gong et al, 2018 ). Cuscino et al identified eight novel miRNAs in osteosarcoma cell lines and their release in exosomes, which demonstrated that these candidate miRNAs could potentially represent biomarkers for osteosarcoma ( Cuscino et al, 2019 ). Yoshida et al reported that the levels of exosomal miR-25-3p were significantly correlated with a poor prognosis of osteosarcoma ( Yoshida et al, 2018 ).…”

Circulating MicroRNAs as Novel Potential Diagnostic Biomarkers for Osteosarcoma: A Systematic Review

“…Many studies on the use of circulating microRNAs as biomarkers in the diagnosis of OS have been carried out and published. They concluded that several microRNAs were found to be differentially expressed-either up-or downregulated [4,9]. Despite the useful number of publications on this subject, there are some inconsistencies between them, due to differences in the detection methods, the analysis of microRNAs expression, etc.…”