CNDP1 Suppresses the Malignant Behavior of Hepatoma Cell via Restricting PI3K-AKT-mTOR Activation.

Abstract

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.