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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2021 | osteosarcoma | Research

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

Authors: Bingsheng Yang, Lutao Li, Ge Tong, Zhirui Zeng, Jianye Tan, Zexin Su, Zhengwei Liu, Jiezhao Lin, Wenwen Gao, Jianping Chen, Sisi Zeng, Guofeng Wu, Lin Li, Shuang Zhu, Qiuzhen Liu, Lijun Lin

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

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.

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Title: Circular RNA circ_001422 promotes the progression and metastasis of osteosarcoma via the miR-195-5p/FGF2/PI3K/Akt axis
Authors: Bingsheng Yang
Lutao Li
Ge Tong
Zhirui Zeng
Jianye Tan
Zexin Su
Zhengwei Liu
Jiezhao Lin
Wenwen Gao
Jianping Chen
Sisi Zeng
Guofeng Wu
Lin Li
Shuang Zhu
Qiuzhen Liu
Lijun Lin
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: osteosarcoma
Metastasis
Osteosarcoma
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-02027-0

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