Exosomal MiRNAs in Osteosarcoma: Biogenesis and Biological Functions

Abstract

MiRNAs are a group of non-coding RNA molecules that function in mRNA translational inhibition via base-pairing with complementary sequences in target mRNA. In oncology, miRNAs have raised great attention due to their aberrant expression and pivotal roles in the pathogenesis of multiple malignancies including osteosarcoma. MiRNAs can be transported by exosome, the nano-extracellular vesicle with a diameter of 30–150 nm. Recently, a growing number of studies have demonstrated that exosomal miRNAs play a critical role in tumor initiation and progression, by exerting multiple biological functions including metastasis, angiogenesis, drug resistance and immunosuppression. In this review, we aim to depict the biogenesis of exosomal miRNAs and summarize the potential diagnostic and therapeutic functions of exosomal miRNAs in osteosarcoma.

Structural Modifications and Novel Protein-Binding Sites in Pre-miR-675—Explaining Its Regulatory Mechanism in Carcinogenesis

“…Since this study identified FUS as the interactor of pre-miR-675, which also contains the above EXOmotif adjacent to FUS protein-binding motif ( Figure 2 G), it is quite possible that the binding of FUS to pre-miR-675 could result in the secretion of the latter into exosomes. Indeed, several studies have identified the exosomal presence of pre-miR-675 in many diseases [ 29 , 30 , 31 ], however, the identification of EXOmotif in pre-miR-675 explains the exosomal properties of pre-miR-675. Lin-28 homolog B (Lin28B) is an evolutionary conserved RNA-binding protein, which can bind to precursor miRNAs and can interfere with their maturation process [ 32 ].…”

Cancer-derived exosomes as novel biomarkers in metastatic gastrointestinal cancer

“…Immune system is the most powerful barrier to cancer metastasis. Massive studies have demonstrated that, within the tumor local inflammatory microenvironment, CDEs can transport proteins similar to parent tumor cells, proinflammatory chemokines, and cytokines, such as IL-35, IL10, TNF-α, IFN-γ, and TGF-β2, genomic DNA, mRNA, and microRNAs to interact with immune cells, including B cells, T cells, natural killer (NK) cells, regulatory T cells (Tregs), and tumor-associated macrophages (TAMs), thus weakening antitumor immune responses and escaping from immune surveillance [ 53 , 54 ]. CDEs can ①influence immune cell maturity: impair DC maturation by influencing IL-6 expression [ 55 ], ②inhibit immune cell proliferation: impact T cell proliferation by targeting TGF-β and NK cells proliferation and cytotoxic functions via downregulating NK associated proteins [ 56 , 57 ], ③inhibit the functions necessary for antitumor responses, ④induce apoptosis of activated immune cells, ⑤suppress immune cells activity, ⑥interfere with monocyte differentiation, ⑦skew the differentiation of myeloid precursor cells, ⑧polarize immune cells into tumor-promoting phenotypes [ 53 ].…”

Novel insights into the multifaceted roles of m6A-modified LncRNAs in cancers: biological functions and therapeutic applications

“…It is an aggressive tumor that occurs from primitive transformed cells of mesenchymal origin that exhibits osteoblastic differentiation and produces malignant osteoid. Till now, because of the lack of efficient early diagnosis, the 5-year-survival rate and prognosis of osteosarcoma patients still remain unsatisfactory [ 184 ]. Though osteosarcoma is one of the earliest identified hominin malignancies, there is very few lack specific tumor markers for osteosarcoma.…”