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Published on: May 10, 2024
KLF5‑mediated expression of CARD11 promotes the progression of gastric cancer
Qiusen Li1, Sheng Li1, Zongxian Li1
1Department of Gastroenterology, The Second People's Hospital of Wuhu, Wuhu, Anhui 241000, P.R. China.
Insights
Caspase recruitment domain-containing protein 11 (CARD11) drives gastric cancer growth and metastasis. The transcription factor Krüppel-like factor 5 (KLF5) upregulates CARD11, promoting tumor progression and activating the mTOR pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Caspase recruitment domain-containing protein 11 (CARD11) is implicated in various cancers.
- Its specific role and regulatory mechanisms in gastric cancer remain to be fully elucidated.
Purpose of the Study:
- To investigate the function and mechanism of CARD11 in gastric cancer.
- To explore the regulatory relationship between CARD11 and Krüppel-like factor 5 (KLF5).
Main Methods:
- Analysis of CARD11 expression and patient survival data.
- In vitro experiments involving CARD11 silencing and KLF5 overexpression in gastric cancer cells.
- Assessment of cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and signaling pathways (mTOR).
Main Results:
- High CARD11 expression correlates with poor prognosis in gastric cancer.
- CARD11 inhibition suppressed proliferation, migration, invasion, and EMT, while inducing cell cycle arrest.
- KLF5 was identified as a positive regulator of CARD11 transcription.
- KLF5 overexpression counteracted the effects of CARD11 silencing, promoting proliferation, migration, invasion, and EMT.
Conclusions:
- CARD11 promotes gastric cancer progression by enhancing proliferation, migration, invasion, and EMT.
- The KLF5-CARD11 axis plays a critical role in gastric cancer development.
- CARD11 interference inhibits gastric cancer growth and metastasis, partly through the mTOR pathway.
Abstract:
Caspase recruitment domain-containing protein 11 (CARD11) has been reported as functioning in multiple types of cancers. In the present study, the role and mechanism of CARD11 in gastric cancer was investigated. First, CARD11 expression in gastric cancer tissues and the association of CARD11 with overall survival were analyzed by the encyclopedia of RNA interactomes database. CARD11 expression in gastric cancer cells was detected by western blotting and reverse transcription-quantitative PCR analyses. After CARD11 silencing, cell proliferation was evaluated by Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine staining and flow cytometry analysis. Wound healing and Transwell assays were used to measure the capacities of cell migration and invasion. Additionally, the expression levels of epithelial-mesenchymal transition (EMT)-related proteins and mTOR-related proteins were detected by western blot analysis. HumanTFDB predicted the binding of the transcription factor Krüppel-like factor 5 (KLF5) to the CARD11 promoter, which was confirmed by dual luciferase reporter and chromatin immunoprecipitation assays. To explore the regulatory effects between KLF5 and CARD11, KLF5 was overexpressed to perform the rescue experiments in gastric cancer cells with CARD11 silencing. Results revealed that CARD11 was highly expressed in gastric cancer and was associated with poor prognosis. CARD11 interference inhibited the proliferation of gastric cancer cells and induced cell cycle arrest. Additionally, CARD11 silencing suppressed the migration, invasion and EMT of gastric cancer cells, accompanied by upregulated E-cadherin expression and downregulated N-cadherin and vimentin expression. Moreover, the transcription factor KLF5 positively regulated the transcription of CARD11 in gastric cancer. KLF5 overexpression reversed the effects of interference of CARD11 expression in gastric cancer cells to promote their proliferation, migration, invasion and EMT. KLF5 overexpression also led to a reduction in cell cycle arrest. Finally, interference of CARD11 expression suppressed the mTOR pathway, which was activated by KLF5. In conclusion, KLF5-mediated CARD11 promoted the proliferation, migration and invasion of gastric cancer cells.
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