Circular RNA circFIRRE drives osteosarcoma progression and metastasis through tumorigenic-angiogenic coupling

Abstract

Background Disappointing clinical efficacy of standard treatment has been proven in refractory metastatic osteosarcoma, and the emerging anti-angiogenic regimens are still in the infantile stage. Thus, there is an urgent need to develop novel therapeutic approach for osteosarcoma lung metastasis. Methods circFIRRE was selected from RNA-sequencing of 4 matched osteosarcoma and adjacent samples. The expression of circFIRRE was verified in clinical osteosarcoma samples and cell lines via quantitative real-time polymerase chain reaction (RT-qPCR). The effect of circFIRRE was investigated in cell lines in vitro models, ex vivo models and in vivo xenograft tumor models, including proliferation, invasion, migration, metastasis and angiogenesis. Signaling regulatory mechanism was evaluated by RT-qPCR, Western blot, RNA pull-down and dual-luciferase reporter assays. Results In this article, a novel circular RNA, circFIRRE (hsa_circ_0001944) was screened out and identified from RNA-sequencing, and was upregulated in both osteosarcoma cell lines and tissues. Clinically, aberrantly upregulated circFIRRE portended higher metastatic risk and worse prognosis in osteosarcoma patients. Functionally, in vitro, ex vivo and in vivo experiments demonstrated that circFIRRE could drive primary osteosarcoma progression and lung metastasis by inducing both tumor cells and blood vessels, we call as “tumorigenic-angiogenic coupling”. Mechanistically, upregulated circFIRRE was induced by transcription factor YY1, and partially boosted the mRNA and protein level of LUZP1 by sponging miR-486-3p and miR-1225-5p. Conclusions We identified circFIRRE as a master regulator in the tumorigenesis and angiogenesis of osteosarcoma, which could be purposed as a novel prognostic biomarker and therapeutic target for refractory osteosarcoma.

Hypoxia Inhibitor Combined with Chemotherapeutic Agents for Antitumor and Antimetastatic Efficacy against Osteosarcoma

“…To further investigate the antimetastatic ability of AD@PLGA–PEG NPs in vivo, we established a lung metastasis model by injecting K7M2 cells into BALB/c mice via the tail vein according to a literature method. − The drug administration scheme is shown in Figure A. Tumor-bearing mice were randomly classified into four groups, control, ABZ@PLGA–PEG NPs, DOX@PLGA–PEG NPs, and AD@PLGA–PEG NPs, and the mice were treated every 3 days for a total of 9 treatments.…”

Diagnosis potential of subarachnoid hemorrhage using miRNA signatures isolated from plasma-derived extracellular vesicles

“…In addition, as a novel non-invasive biomarker, extracellular vesicle expression of miR-193b-3p is upregulated in HeLa cancer cells and directly targets HDAC3 (Lin et al, 2018;Meng et al, 2018); it also attenuates neuroinflammation in early brain injury after aSAH in mice (Lai et al, 2020). miR-486-3p was correlated with central nervous system maturation, inflammation, and cancer (Li et al, 2021;Li et al, 2022;Yu et al, 2022). miR-486-3p has been identified as a candidate diagnostic marker for oral tongue squamous cell carcinoma; in addition, it plays a vital role in neuronal differentiation and central nervous system maturation in the brain (Chen et al, 2017;Yu et al, 2018).…”

“…miR-486-3p was correlated with central nervous system maturation, inflammation, and cancer ( Li et al, 2021 ; Li et al, 2022 ; Yu et al, 2022 ). miR-486-3p has been identified as a candidate diagnostic marker for oral tongue squamous cell carcinoma; in addition, it plays a vital role in neuronal differentiation and central nervous system maturation in the brain ( Chen et al, 2017 ; Yu et al, 2018 ).…”

CircXPO1 Promotes Glioblastoma Malignancy by Sponging miR-7-5p

“…circRNAs, a new class of ncRNAs, are also highly enriched in the brain tissue, suggesting their potential roles in brain physiology and pathology [ 29 ]. With the advent of high-throughput circRNA sequencing, circRNAs have been found to be involved in a variety of physiological phenomena, such as angiogenesis [ 30 ], autophagy [ 31 ], apoptosis [ 32 ], and inflammation [ 33 ]. Moreover, there are reports for their strong association with brain tumors [ 12 ] and injuries [ 34 ], chronic neurodegenerative diseases [ 6 ], or other neurological disorders, including addiction [ 35 ], schizophrenia [ 36 ], and major depression [ 37 ].…”