AI Article Synopsis
- LZAP, a protein associated with the Cdk5 activator p35, is identified as a tumor suppressor, showing decreased expression in hepatocellular carcinoma (HCC) tissues and cell lines, which correlates with poor patient prognosis.
- Using various laboratory methods, the study established that lower LZAP levels are linked to larger tumor sizes and poorer survival rates, indicating it could serve as an independent prognostic marker.
- Restoring LZAP expression in HCC cell lines and mouse models demonstrated its ability to inhibit cancer cell proliferation, migration, invasion, and tumor growth, highlighting its potential for molecular therapy in HCC.
Article Abstract
Background: LZAP was isolated as a binding protein of the Cdk5 activator p35. LZAP has been highly conserved during evolution and has been shown to function as a tumor suppressor in various cancers. This study aimed to investigate LZAP expression and its prognostic value in hepatocellular carcinoma (HCC). Meanwhile, the function of LZAP in hepatocarcinogenesis was further investigated in cell culture models and mouse models.
Methods: Real-time quantitative PCR, western blot and immunohistochemistry were used to explore LZAP expression in HCC cell lines and primary HCC clinical specimens. The functions of LZAP in the proliferation, colony formation, cell cycle, migration, invasion and apoptosis of HCC cell lines were also analyzed by infecting cells with an adenovirus containing full-length LZAP. The effect of LZAP on tumorigenicity in nude mice was also investigated.
Results: LZAP expression was significantly decreased in the tumor tissues and HCC cell lines. Clinicopathological analysis showed that LZAP expression was significantly correlated with tumor size, histopathological classification and serum α-fetoprotein (AFP). The Kaplan-Meier survival curves revealed that decreasing LZAP expression was associated with poor prognosis in HCC patients. LZAP expression was an independent prognostic marker of overall HCC patient survival in a multivariate analysis. The re-introduction of LZAP expression in the HepG2 and sk-Hep1 HCC cell lines significantly inhibited proliferation and colony formation in the HCC cells and induced G1 phase arrest and apoptosis of the HCC cells in vitro. Restoring LZAP expression in the HCC cell lines also inhibited migration and invasion. In addition, experiments with a mouse model revealed that LZAP overexpression could suppress HCC tumorigenicity in vivo.
Conclusions: Our data suggest that LZAP may play an important role in HCC progression and could be a potential molecular therapy target for HCC.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197520 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026608 | PLOS |
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