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Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA mediated miRNA evasion
Yong-Xi Song1, Jing-Xu Sun1, Jun-Hua Zhao1
1Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City, 110001, China.
Abstract:
Thousands of genes have been well demonstrated to play important roles in cancer progression. As genes do not function in isolation, they can be grouped into "networks" based on their interactions. In this study, we discover a network regulating Claudin-4 in gastric cancer. We observe that Claudin-4 is up-regulated in gastric cancer and is associated with poor prognosis. Claudin-4 reinforce proliferation, invasion, and EMT in AGS, HGC-27, and SGC-7901 cells, which could be reversed by miR-596 and miR-3620-3p. In addition, lncRNA-KRTAP5-AS1 and lncRNA-TUBB2A could act as competing endogenous RNAs to affect the function of Claudin-4. Our results suggest that non-coding RNAs play important roles in the regulatory network of Claudin-4. As such, non-coding RNAs should be considered as potential biomarkers and therapeutic targets against gastric cancer.Non-coding RNAs can modify the expression of proteins in cancer networks. Here the authors reveal a regulatory network in gastric cancer whereby claudin-4 expression is reduced by specific miRNAs, which are in turn bound by specific lncRNAs acting as competing endogenous RNAs (ceRNAs), resulting in increased claudin-4 expression.
Insights
This study reveals a Claudin-4 regulatory network in gastric cancer. Non-coding RNAs, including microRNAs and lncRNAs, are key players, offering potential biomarkers and therapeutic targets for gastric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gene interactions form networks crucial for cancer progression.
- Claudin-4 is implicated in gastric cancer development and patient prognosis.
Purpose of the Study:
- To identify a regulatory network controlling Claudin-4 in gastric cancer.
- To investigate the role of non-coding RNAs in this network.
Main Methods:
- Analysis of Claudin-4 expression and its association with prognosis.
- Investigating the effects of Claudin-4 on cell proliferation, invasion, and epithelial-mesenchymal transition (EMT).
- Assessing the regulatory roles of specific microRNAs (miRNAs) and long non-coding RNAs (lncRNAs).
Main Results:
- Claudin-4 is upregulated in gastric cancer, correlating with poor prognosis.
- Claudin-4 promotes proliferation, invasion, and EMT in gastric cancer cells.
- miR-596 and miR-3620-3p reversed Claudin-4's effects; lncRNA-KRTAP5-AS1 and lncRNA-TUBB2A function as competing endogenous RNAs (ceRNAs).
Conclusions:
- Non-coding RNAs are integral to the Claudin-4 regulatory network in gastric cancer.
- These non-coding RNAs represent potential diagnostic biomarkers and therapeutic targets for gastric cancer.
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