Functional Role of RBP in Osteosarcoma: Regulatory Mechanism and Clinical Therapy

Abstract

Malignant bone neoplasms can be represented by osteosarcoma (OS), which accounts for 36% of all sarcomas. To reduce tumor malignancy, extensive efforts have been devoted to find an ideal target from numerous candidates, among which RNA-binding proteins (RBPs) have shown their unparalleled competitiveness. With the special structure of RNA-binding domains, RBPs have the potential to establish relationships with RNAs or small molecules and are considered regulators of different sections of RNA processes, including splicing, transport, translation, and degradation of RNAs. RBPs have considerable significant roles in various cancers, and experiments revealed that there was a strong association of RBPs with tumorigenesis and tumor cell progression. Regarding OS, RBPs are a new orientation, but achievements in hand are noteworthy. Higher or lower expression of RBPs was first found in tumor cells compared to normal tissue. By binding to different molecules, RBPs are capable of influencing tumor cell phenotypes through different signaling pathways or other axes, and researches on medical treatment have been largely inspired. Exploring the prognostic and therapeutic values of RBPs in OS is a hotspot where diverse avenues on regulating RBPs have achieved dramatical effects. In this review, we briefly summarize the contribution of RBPs and their binding molecules to OS oncogenicity and generally introduce distinctive RBPs as samples. Moreover, we focus on the attempts to differentiate RBP's opposite functions in predicting prognosis and collect possible strategies for treatment. Our review provides forwards insight into improving the understanding of OS and suggests RBPs as potential biomarkers for therapies.

Figure 1

Diverse function of RBPs in OS progression.

Figure 2

Mechanisms of HuR in regulating OS progression. Red arrows represent positive regulation, while blue ones are negative. (a) HuR binds to HMGA1 and miR-142-3p to promote OS cell proliferation and EMT while reduce cell apoptosis at the same time. (b) LncRNA XIST combined AGO2 and HuR to promote EMT and migration of OS. (c) HuR was positively related to Bcl-2 overexpression and thus reduce apoptosis. B4GALT1-AS1 was contributed to the delivery of HuR from nucleus to cytoplasm and upregulated YAP expression that promotes OS cell proliferation, migration and invasion, EMT, and stemness. The effect of Adriamycin was observed attenuated when YAP overexpressed. (d) DUXAP10 was largely expressed in nucleus and was demonstrated to bind HuR and SOX18 to promote migration and invasion and reduce apoptosis of OS cells.

Figure 3

Multiple functions of IGF2BPs in reducing OS malignancy: regulatory mechanism, medicine therapy, and prognosis. Red arrows represent positive regulation, while blue ones are negative.