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Downregulated pseudogene CTNNAP1 promote tumor growth in human cancer by downregulating its cognate gene CTNNA1
Xiangjian Chen1,2, Hua Zhu3, Xiaoli Wu4
1Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China.
Abstract:
Accumulating evidence indicates that deregulation of cancer-associated pseudogene is involved in the pathogenesis of cancer. In the study, we demonstrated that pseudogene CTNNAP1, for the CTNNA1 gene, was dysregulated in colorectal cancer and the degree of dysregulation was remarkably associated with tumor node metastasis (TNM) stage (P<0.05). The mechanistic experiments revealed that pseudogene CTNNAP1 played a pivotal role in the regulation of its cognate gene CTNNA1 by competition for microRNA-141. Moreover, gain-of-function approaches showed that overexpression of CTNNAP1 or CTNNA1 significantly inhibited cell proliferation and tumor growth in vitro and in vivo by inducing G0/G1 cell cycle arrest. Our findings add a new regulatory circuit via competing endogenous RNA (ceRNA) cross-talk between pseudogene CTNNAP1 and its cognate gene CTNNA1, and provide new insights into potential diagnostic biomarker for monitoring human colorectal cancer.
Insights
Pseudogene CTNNAP1 is dysregulated in colorectal cancer, correlating with tumor stage. Its overexpression inhibits cancer growth by regulating its cognate gene CTNNA1, offering a potential diagnostic biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Deregulation of cancer-associated pseudogenes contributes to cancer development.
- Pseudogenes are increasingly recognized for their roles in disease pathogenesis.
Purpose of the Study:
- To investigate the role of pseudogene CTNNAP1 in colorectal cancer.
- To elucidate the regulatory mechanism of CTNNAP1 and its cognate gene CTNNA1.
- To explore the potential of CTNNAP1 as a diagnostic biomarker for colorectal cancer.
Main Methods:
- Analysis of pseudogene CTNNAP1 dysregulation in colorectal cancer tissues.
- Mechanistic studies involving microRNA-141 and competing endogenous RNA (ceRNA) interactions.
- Gain-of-function experiments to assess the impact of CTNNAP1 and CTNNA1 overexpression on cell proliferation and tumor growth in vitro and in vivo.
Main Results:
- Pseudogene CTNNAP1 was found to be dysregulated in colorectal cancer, with significant association with tumor node metastasis (TNM) stage.
- CTNNAP1 regulates its cognate gene CTNNA1 through competition for microRNA-141.
- Overexpression of CTNNAP1 or CTNNA1 inhibited colorectal cancer cell proliferation and tumor growth by inducing G0/G1 cell cycle arrest.
Conclusions:
- A novel competing endogenous RNA (ceRNA) regulatory circuit involving pseudogene CTNNAP1 and its cognate gene CTNNA1 was identified in colorectal cancer.
- Pseudogene CTNNAP1 plays a significant role in colorectal cancer pathogenesis.
- CTNNAP1 presents potential as a diagnostic biomarker for monitoring human colorectal cancer.
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