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CNDP1 Suppresses the Malignant Behavior of Hepatoma Cell via Restricting PI3K-AKT-mTOR Activation
Youwen Du1, Linxin Pan1, Wenchen Zhang1
1School of Life Sciences, Anhui Medical University, Hefei, Anhui, China.
Introduction:
Hepatocellular carcinoma (HCC) is a global health problem with increasing morbidity and mortality, and exploring the diagnosis and treatment of HCC at the gene level has become a research hotspot in recent years. As the rate-limiting enzyme of carnosine hydrolysis, CNDP1 participates in the progress of many diseases, but its function in HCC has not been fully elucidated.
Methods:
This study firstly screened differentially expressed genes from the biochip related to HCC by bioinformatic analysis, and CNDP1 was finally selected for in-depth study. Then the bioinformatics analysis results were validated by detecting the expression of CNDP1 in human HCC samples and hepatoma cell lines. Furthermore, the effect of CNDP1 on the malignant behavior of hepatoma cell lines were assessed using MTT colorimetric assay, EdU staining assay, colony formation, wound-healing assay and transwell, and the molecular mechanism was also preliminarily explored.
Results:
This study found that CNDP1 expression was decreased significantly in human HCC tissues and cell lines, and its overexpression could significantly suppress cell proliferation, migration and invasion of hepatoma cell lines. Mechanistically the GeneMANIA database predicted that CNDP1 could interact with various proteins involved in regulating PI3K-AKT-mTOR signaling pathway. Furthermore, this study showed that CNDP1 overexpression could effectively inhibit the activation of PI3KAKT- mTOR signaling pathways, more significantly, inhibition of PI3K-AKT-mTOR signaling pathway could disrupt the anti-cancer effect of CNDP1 on HCC.
Conclusion:
This study confirm that CNDP1 expression is decreased significantly in HCC, and has potential anti-cancer activity, this discovery provides a cytological basis for further understanding the biological function of CNDP1 and diagnosis and gene therapy of HCC in the future.
Insights
The enzyme CNDP1 is significantly decreased in hepatocellular carcinoma (HCC). Overexpressing CNDP1 suppresses HCC cell growth and migration, offering potential for gene therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) presents a significant global health challenge with rising mortality.
- Investigating gene-level mechanisms is crucial for advancing HCC diagnosis and treatment.
- The role of CNDP1, an enzyme in carnosine hydrolysis, in HCC remains largely unexplored.
Purpose of the Study:
- To investigate the role and mechanism of CNDP1 in hepatocellular carcinoma.
- To identify CNDP1 as a potential therapeutic target for HCC.
Main Methods:
- Bioinformatic analysis to screen differentially expressed genes in HCC.
- Validation of CNDP1 expression in HCC tissues and cell lines.
- Assessment of CNDP1's impact on hepatoma cell malignant behaviors (proliferation, migration, invasion) using various assays.
- Exploration of the molecular mechanism involving the PI3K-AKT-mTOR pathway.
Main Results:
- CNDP1 expression is significantly downregulated in HCC tissues and cell lines.
- Overexpression of CNDP1 inhibits proliferation, migration, and invasion of HCC cells.
- CNDP1 interacts with proteins in the PI3K-AKT-mTOR signaling pathway.
- CNDP1 overexpression suppresses PI3K-AKT-mTOR pathway activation, and pathway inhibition counteracts CNDP1's anti-cancer effects.
Conclusions:
- CNDP1 exhibits significant downregulation in HCC and possesses anti-cancer properties.
- This study provides a foundation for understanding CNDP1's biological function in HCC.
- CNDP1 presents potential as a diagnostic marker and therapeutic target for HCC gene therapy.
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