Therapeutic potential of targeting PCLAF in endometrial cancer: Insights from Wnt/β-catenin and P53 regulatory mechanisms.

BACKGROUND

Endometrial cancer (EC), a widespread gynecological malignancy, has limited therapeutic options, particularly in patients with advanced, metastatic, or recurrent disease. PCLAF, a proliferation-related protein, is overexpressed in several tumors; however, its role and mechanism in EC remain largely unknown.

METHODS

Ten hub genes in EC were identified and predicted through bioinformatics analyses. The expression of PCLAF in EC was validated using molecular biology technology, while its function was investigated using in vitro proliferation, cell cycle, migration, and apoptosis assays. Mechanistically, the transcriptome and proteome sequencing revealed potential regulatory pathways for PCLAF in EC. Finally, experiments on animals were executed to test the Ishikawa cell growth in vivo.

RESULTS

PCLAF exhibited high expression in both EC cells and tissues. Silencing PCLAF significantly impaired cell proliferation, migration and invasion, blocked G1 phase progression of the cell cycle and activated apoptosis. Sequencing results and western blot analysis confirmed that knockdown of EC cells inhibits the Wnt/β-catenin pathway and activates the p53 pathway. The in vivo results confirmed that PCLAF knockdown effectively inhibited EC cell growth.

CONCLUSION

In conclusion, our findings suggest that silencing PCLAF hinders EC progression by suppressing the Wnt/β-catenin pathway and activating the p53 signaling pathway. This insight suggested that targeting PCLAF may offer a new therapeutic avenue for EC treatment.