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

作者：Bingsheng Yang, Lutao Li, Tong Ge, 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 · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2021 · DOI：10.1186/s13046-021-02027-0 · 被引用次数：160 · 研究领域：Circular RNAs in diseases、MicroRNA in disease regulation、Sarcoma Diagnosis and Treatment

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 a...