CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner
Shengkui Qiu, Bowen Li, Yiwen Xia, Zhe Xuan, Zheng Li, Li Xie, Chao Gu, Jialun Lv, Lu Chen, Tianlu Jiang, Lang Fang, Penghui Xu, Jing Yang, Ying Li, Zetian Chen, Lu Zhang, Linjun Wang, Diancai Zhang, Hao Xu, Weizhi Wang, Zekuan Xu
Abstract
Circular RNAs (circRNAs) play vital regulatory roles in the progression of multiple cancers. In our study, transcriptome analysis and self-organizing maps (SOM) were applied to screen backbone circRNAs in gastric cancer (GC). Upon validation of the expression patterns of screened circRNAs, gain- and loss-of-function assays were performed in vitro and in vivo. Underlying mechanisms were investigated using RNA pull-down, luciferase reporter assay and RNA immunoprecipitation. The expression of circTHBS1 was significantly increased in GC and associated with poor prognosis. CircTHBS1 facilitated the malignant behavior and epithelial-to-mesenchymal transition of GC cells. Mechanistically, circTHBS1 sponged miR-204-5p to promote the expression of Inhibin Subunit Beta A (INHBA). Moreover, circTHBS1 could enhance the HuR-mediated mRNA stability of INHBA, which subsequently activated the TGF-β pathway. Our research identified circTHBS1 as an oncogenic circRNA that enhances GC malignancy by elevating INHBA expression, providing new insight and a feasible target for the diagnosis and treatment of GC.