Circular RNA circ_001422 promotes the progression and metastasis of osteosarcoma via the miR-195-5p/FGF2/PI3K/Akt axis

Abstract

Background Circular RNAs (circRNAs) are involved in diverse processes that drive cancer development. However, the expression landscape and mechanistic function of circRNAs in osteosarcoma (OS) remain to be studied. Methods Bioinformatic analysis and high-throughput RNA sequencing tools were employed to identify differentially expressed circRNAs between OS and adjacent noncancerous tissues. The expression level of circ_001422 in clinical specimens and cell lines was measured using qRT-PCR. The association of circ_001422 expression with the clinicopathologic features of 55 recruited patients with OS was analyzed. Loss- and gain-of-function experiments were conducted to explore the role of circ_001422 in OS cells. RNA immunoprecipitation, fluorescence in situ hybridization, bioinformatics database analysis, RNA pulldown assays, dual-luciferase reporter assays, mRNA sequencing, and rescue experiments were conducted to decipher the competitive endogenous RNA regulatory network controlled by circ_001422. Results We characterized a novel and abundant circRNA, circ_001422, that promoted OS progression. Circ_001422 expression was dramatically increased in OS cell lines and tissues compared with noncancerous samples. Higher circ_001422 expression correlated with more advanced clinical stage, larger tumor size, higher incidence of distant metastases and poorer overall survival in OS patients. Circ_001422 knockdown markedly repressed the proliferation and metastasis and promoted the apoptosis of OS cells in vivo and in vitro, whereas circ_001422 overexpression exerted the opposite effects. Mechanistically, competitive interactions between circ_001422 and miR-195-5p elevated FGF2 expression while also initiating PI3K/Akt signaling. These events enhanced the malignant characteristics of OS cells. Conclusions Circ_001422 accelerates OS tumorigenesis and metastasis by modulating the miR-195-5p/FGF2/PI3K/Akt axis, implying that circ_001422 can be therapeutically targeted to treat OS.

circ-RANGAP1/MicroRNA-542-3p/Myosin Regulatory Light Chain Interacting Protein Axis Modulates the Osteosarcoma Cell Progression

“…The lower chamber was fulfilled with 600 μ L DMEM containing 10% FBS as an attractant. After 24 h of culture, cells were fixed on the lower surface with paraformaldehyde (4%), stained with crystal violet (0.1%), and viewed using inverted light microscopy [ 11 ].…”

“…Control probes and biotinylated circ-RANGAP1 and miR-542-3p probes (RiboBio, Guangzhou, China) were incubated with C-1 magnetic beads (LifeTechnologies, USA) for 2 h. Cell lysates were incubated with biotinylated circ-RANGAP1 and miR-542-3p probes, and RNA was extracted using RNeasy Mini Kit (Qiagen, USA), followed by measurement of circ-RANGAP1 and miR-542-3p expressions in the RNA complex [ 11 ].…”

Development and Validation of Novel Prognostic Models for Immune-Related Genes in Osteosarcoma

“…Next, eight hub genes were identified by Cytoscape: CXCR4, PDGFRB, CXCL10, B2M, CD86, CSF1R, TYROBP, and FGF2. CXCR4 ( Zhu et al, 2018 ), CSF1R ( Smeester et al, 2020 ), and FGF2 ( Yang et al, 2021 ) have been shown to promote OS progression. PDGFRB ( Liu et al, 2018 ), CXCL10 ( Niu et al, 2020 ), CD86 ( Jin et al, 2019 ), and TYROBP ( Wang et al, 2021 ) were identified as hub genes according to bioinformatic analysis.…”

Long Noncoding RNA LEMD1-AS1 Increases LEMD1 Expression and Activates PI3K-AKT Pathway to Promote Metastasis in Oral Squamous Cell Carcinoma

“…To determine the role of lncRNAs and their target genes in cervical LN metastasis of OSCC, we identified the differentially expressed mRNAs and lncRNAs between primary OSCC samples with and without regional LN metastasis, since the expression pattern of primary tissues was similar to that of metastatic tissues according to the single cell sequencing result of head and neck squamous cell carcinoma in 2017 [ 15 ]. The DERNAs were enriched in GO components and KEGG pathways associated with tumor progression, migration and invasion, such as cell adhesion [ 16 , 17 ], channel and receptor activity [ 18 – 20 ], cAMP signaling pathway [ 21 ], PI3K-AKT signaling pathway [ 22 , 23 ], cytokine-cytokine receptor interaction, and CAMs [ 24 ]. The DElncRNA-DEmRNA network was subsequently constructed, and LEMD1-AS1 and its antisense mRNA LEMD1 were identified as a relevant pair in OSCC.…”