Exosomes containing differential expression of microRNA and mRNA in osteosarcoma that can predict response to chemotherapy

Abstract

A major challenge in osteosarcoma (OS) is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent. We developed a profiling strategy for serum exosomal microRNAs and mRNAs in OS patients with differential chemotherapeutic responses. Twelve miRNAs were up regulated and 18 miRNAs were under regulated significantly in OS patient with poor chemotherapeutic response when compared with those in good chemotherapeutic response (p<0.05). In addition, miR-124, miR133a, miR-199a-3p, and miR-385 were validated and significantly reduced in poorly responded patients with an independent OS cohort. While miR-135b, miR-148a, miR-27a, and miR-9 were significantly over expressed in serum exosomes. Bioinformatic analysis by DIANA-mirPath demonstrated that Proteoglycans in cancer, Hippo signaling pathway, Pathways in cancer, Transcriptional misregulation in cancer, PI3K-Akt signaling pathway, Ras signaling pathway, Ubiquitin mediated proteolysis, Choline metabolism in cancer were the most prominent pathways enriched in quantiles with the miRNA patterns related to poor chemotherapeutic response. Messenger RNAs(mRNAs) includingAnnexin2, Smad2, Methylthioadenosine phosphorylase (MTAP), Cdc42-interacting protein 4 (CIP4), Pigment Epithelium-Derived Factor (PEDF), WW domain-containing oxidoreductase (WWOX), Cell division cycle 5-like (Cdc5L), P27 were differentially expressed in exosomes in OS patients with different chemotherapeutic response. These data demonstrated that exosomal RNA molecules are reliable biomarkers in classifying osteosarcoma with different chemotherapy sensitivity.

Exploring the RNA landscape of endothelial exosomes

“…One very interesting observation highlighted by this work is the peculiar distribution of mRNA in cells and exosomes. Messenger RNAs have been earlier found in exosomes and some of them are suggested to be powerful biomarkers (Provencio et al 2017;Xu et al 2017). Other studies have shown that mRNAs are transported from the parent to the recipient cell via exosomes remaining active (Lobb et al 2017).…”

Bone marrow‐derived mesenchymal stem cell‐derived exosomal microRNA‐208a promotes osteosarcoma cell proliferation, migration, and invasion

“…Zhang et al, 2015). For example, exosomal miRs have been reported to be associated with different responses to chemotherapy in osteosarcoma patients (Xu et al, 2017). Evidence has clearly shown that the miR-208 family is closely related to the development of some cardiac diseases, including myocardial infarction, cardiac fibrosis, and heart failure (Huang & Li, 2015).…”

Maternal and umbilical cord serum‐derived exosomes enhance endothelial cell proliferation and migration

“…Recently, serum exosomal miRNA profiles of different disease were carried out. The miRNAs present varied greatly between different studies, ranging from 164 serum exosomal miRNAs in cancer patients to 584 distinct miRNAs in serum exosomes per normal sample (19)(20)(21). This phenomenon may be attributed to the different platforms used or to the specific physical environment created by specific diseases or conditions.…”