癌症研究
生物
车站3
转移
细胞生长
信号转导
自分泌信号
核糖核酸
基因
细胞生物学
癌症
细胞培养
遗传学
作者
Hui Li,Tian Lan,Hailing Liu,Chang Liu,Junlong Dai,Lin Xu,Yunshi Cai,Guimin Hou,Kunlin Xie,Mingheng Liao,Jiaxin Li,Jiwei Huang,Kefei Yuan,Genshu Wang,Yong Zeng,Hong Wu
出处
期刊:Hepatology
[Wiley]
日期:2021-11-10
卷期号:75 (6): 1402-1419
被引量:69
摘要
Abstract Background and Aims IL‐6–induced tumor progression has been well established through the induction of antiapoptotic and proliferative genes. However, whether other mechanisms such as IL‐6 regulation of circular RNAs (circRNAs) may also contribute to tumor development remains unknown. Approach and Results High‐throughput RNA sequencing was used to identify the differentially expressed circRNAs on IL‐6 stimulation in intrahepatic cholangiocarcinoma (ICC) cells. CircRNA GGNBP2 (derived from ggnbp2 gene, termed as cGGNBP2) was up‐regulated by IL‐6 treatment in a time and concentration‐dependent manner. The biogenesis of cGGNBP2 was regulated by RNA‐binding protein DEx‐H Box Helicase 9, which was also mediated by IL‐6 exposure. Mass spectrometry and western blotting identified a protein cGGNBP2‐184aa encoded by cGGNBP2. cGGNBP2‐184aa promoted ICC cell proliferation and metastasis in vitro and in vivo. Mechanistically, cGGNBP2‐184aa directly interacted with signal transducers and activators of transduction‐3 (STAT3), phosphorylated STAT3 Tyr705 , and played a positive regulatory role in modulating IL‐6/STAT3 signaling. IL‐6/cGGNBP2‐184aa/STAT3 formed a positive feedback loop to sustain constitutive activation of IL‐6/STAT3 signaling. Elevated cGGNBP2 expression was correlated with poor prognosis of patients with ICC and was identified as an independent risk factor for patient prognosis. Conclusions Our study demonstrates that cGGNBP2‐184aa, a protein encoded by IL‐6–induced cGGNBP2, formed a positive feedback loop to facilitate ICC progression and may serve as an auxiliary target for clinical IL‐6/STAT3‐targeting treatments in ICC.
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