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- Title
Downregulated circRNA_CDKN1A promotes gallbladder cancer progression through activation of the NF‐κB pathway.
- Authors
Hu, Bin; Yang, Hui; Wang, Yan; Cao, Yi; Zhou, Rongping; Yang, Dong
- Abstract
This study uncovered the potential clinical value and molecular driving mechanisms of circular RNAs (circRNAs) in gallbladder cancer (GBC). Differentially expressed circRNAs in GBC cells were screened by high‐throughput sequencing. CircRNA_CDKN1A (circBase ID: hsa_circ_0076194) was knocked out in BGC‐SD cells through transfection with sh‐circRNA_CDKN1A. Then, proliferation was investigated via CCK8 and EdU assays, apoptosis via flow cytometry, migration via wound healing assays, and invasion via Transwell assays. Bioinformatics analysis of circRNA_CDKN1A‐related signaling pathways was performed using MetScape and g:Profiler. Results showed that the knockdown of circRNA_CDKN1A enhanced the proliferation, migration, and invasion of GBC cells and inhibited apoptosis. In addition, knocking out circRNA_CDKN1A promoted GBC cell proliferation and enhanced the dry indices of the OCT4 protein and CD34 expression levels. The knockdown of circRNA_CDKN1A activated the epithelial–mesenchymal transition pathway. Bioinformatics analysis revealed that the biological role of circRNA_CDKN1A in GBC cells involved the NF‐κB pathway. LY2409881, which is an NF‐κB inhibitor, reversed the effects induced by the knockdown of circRNA_CDKN1A in GBC‐SD cells. In summary, the knockdown of circRNA_CDKN1A promoted the progression of GBC by activating the NF‐κB signaling pathway. For the first time, this study revealed the mechanism of circRNA_CDKN1A‐mediated regulatory action in GBC and identified the newly discovered circRNA_CDKN1A–NF‐κB signaling axis as a potentially important candidate for clinical therapy and prognostic diagnosis of GBC. Significance statement: The purpose of this study was to uncover the potential clinical value and molecular mechanisms of circular RNAs (circRNAs) in gallbladder cancer (GBC). CircRNA_CDKN1A was significantly and highly expressed by high‐throughput sequencing. Results showed that the knockdown of circRNA_CDKN1A enhanced the proliferation, migration, and invasion of GBC cells and inhibited apoptosis. After circRNA_CDKN1A was knocked down, the epithelial–mesenchymal transition pathway was activated. Bioinformatics analysis revealed that the biological role of circRNA_CDKN1A in GBC cells may involve the NF‐κB pathway. LY2409881, an inhibitor of NF‐κB, reversed the deterioration of GBC‐SD cells caused by decreased circRNA_CDKN1A expression. In summary, circRNA_CDKN1A promoted the progression of GBC by activating the NF‐κB signaling pathway.
- Subjects
GALLBLADDER cancer; CIRCULAR RNA; CANCER invasiveness; CD34 antigen; EPITHELIAL-mesenchymal transition
- Publication
Cell Biochemistry & Function, 2024, Vol 42, Issue 2, p1
- ISSN
0263-6484
- Publication type
Article
- DOI
10.1002/cbf.3952