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.
【초록키워드】 Treatment, Transcriptome, Cancer, Diagnosis, progression, in vitro, RNA, Regulatory, cells, cancers, Research, pathway, Beta, in vivo, reporter, expression, mechanism, TGF-β, Analysis, malignancy, poor prognosis, loss-of-function, immunoprecipitation, backbone, expression pattern, mRNA stability, ENhance, significantly increased, inhibin, performed, investigated, applied, screened, activated, facilitated, promote, feasible, pull-down, Circular, INHBA, oncogenic, 【제목키워드】 stability, cancer progression, mRNA expression, INHBA,