CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner

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...

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Published in:Cell death & disease 2022-03, Vol.13 (3), p.266-266, Article 266
Main Authors: Qiu, Shengkui, Li, Bowen, Xia, Yiwen, Xuan, Zhe, Li, Zheng, Xie, Li, Gu, Chao, Lv, Jialun, Lu, Chen, Jiang, Tianlu, Fang, Lang, Xu, Penghui, Yang, Jing, Li, Ying, Chen, Zetian, Zhang, Lu, Wang, Linjun, Zhang, Diancai, Xu, Hao, Wang, Weizhi, Xu, Zekuan
Format: Article
Language:English
Subjects:
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Antibodies
Biochemistry
Biomedical and Life Sciences
Cell Biology
Cell Culture
Cell Line, Tumor
Cell Proliferation - genetics
Gastric cancer
Gene expression
Gene Expression Regulation, Neoplastic - genetics
Humans
HuR protein
Immunology
Immunoprecipitation
Inhibin
Inhibin-beta Subunits
Life Sciences
Malignancy
Mesenchyme
MicroRNAs - genetics
MicroRNAs - metabolism
mRNA stability
RNA, Circular - genetics
RNA, Messenger - genetics
Stomach Neoplasms - pathology
Thrombospondin 1
Transcriptomes
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Summary: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.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-022-04720-0