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CircCNIH4 inhibits gastric cancer progression via regulating DKK2 and FRZB expression and Wnt/β-catenin pathway
Qi Shi1, Chuanwen Zhou1, Rui Xie1
1Department of Gastroenterology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, No. 1, West Huanghe Road, Huaian, 223300, Jiangsu, China.
Background:
Circular RNAs (circRNAs) have been reported to play an important role in tumor progression in various cancer types, including gastric cancer. The aim of this study was to investigate the role of circCNIH4 (hsa_circ_0000190) in gastric cancer and the underlying mechanism.
Methods:
The expression levels of circCNIH4 and Wnt antagonist genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of β-catenin, Ki67, Dickkopf 2 (DKK2) and Frizzled related protein (FRZB) were measured by western blot. Ectopic overexpression or knockdown of circCNIH4, proliferation, apoptosis, migration and invasion by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry and transwell assay in vitro, and in vivo experiment, were employed to assess the role of circCNIH4 in gastric cancer.
Results:
CircCNIH4 was downregulated in gastric cancer tissues and cells. Overexpression of circCNIH4 inhibited gastric cancer cell proliferation, migration and invasion and promoted apoptosis by inactivating Wnt/β-catenin pathway in vitro. CircCNIH4 induced the expression of DKK2 and FRZB in gastric cancer cells. Moreover, silencing of DKK2 or FRZB reversed circCNIH4 overexpression-mediated effects on gastric cancer cells. Additionally, circCNIH4 suppressed tumor growth via regulating DKK2 and FRZB expression in gastric cancer in vivo.
Conclusion:
Our study demonstrated that circCNIH4 played a tumor-inhibiting role through upregulating DKK2 and FRZB expression and suppressing Wnt/β-catenin pathway in gastric cancer, which might provide a potential biomarker for the diagnosis and treatment of gastric cancer.
Insights
Circular RNAs (circRNAs) like circCNIH4 inhibit gastric cancer progression. Upregulating circCNIH4 increases DKK2 and FRZB, suppressing the Wnt/β-catenin pathway, offering a potential diagnostic and therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are implicated in tumor progression across various cancers, including gastric cancer.
- Gastric cancer remains a significant global health concern, necessitating novel therapeutic targets and biomarkers.
- Understanding the specific roles of circRNAs in gastric cancer is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of circCNIH4 (hsa_circ_0000190) in gastric cancer.
- To elucidate the underlying molecular mechanisms by which circCNIH4 influences gastric cancer.
- To assess the potential of circCNIH4 as a biomarker for gastric cancer diagnosis and treatment.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) for gene expression analysis.
- Western blot to measure protein levels of key pathway components and proliferation markers.
- In vitro (cell culture) and in vivo (animal models) experiments to assess functional roles in proliferation, apoptosis, migration, and invasion.
Main Results:
- CircCNIH4 expression was significantly downregulated in gastric cancer tissues and cells.
- Overexpression of circCNIH4 inhibited gastric cancer cell proliferation, migration, and invasion, while promoting apoptosis.
- CircCNIH4 inactivated the Wnt/β-catenin pathway by upregulating Dickkopf 2 (DKK2) and Frizzled related protein (FRZB) expression, suppressing tumor growth both in vitro and in vivo.
Conclusions:
- CircCNIH4 acts as a tumor suppressor in gastric cancer.
- Upregulation of circCNIH4 inhibits gastric cancer progression by enhancing DKK2 and FRZB expression and suppressing the Wnt/β-catenin pathway.
- CircCNIH4 holds promise as a potential biomarker for the diagnosis and treatment of gastric cancer.
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