PLAC1 augments the malignant phenotype of cervical cancer through the mTOR/HIF-1α/snail signaling pathway.

Aims: This study investigated the molecular mechanisms of placenta-specific protein 1 (PLAC1) in cervical cancer (CCa), aiming to elucidate its role in tumorigenesis through in vitro and in vivo experiments.

Materials and methods: CCa cell lines with overexpressed or silenced PLAC1 were established to evaluate its impact on cell cycle, apoptosis and the expression of key proteins in the PLAC1/mTOR/HIF-1α/Snail signaling pathways. Functional assays were conducted to assess the influence of the PLAC1/mTOR/HIF-1α/Snail regulatory pathway on cell proliferation, migration and invasion. The role of the mTOR signaling pathway in PLAC1-mediated modulation of CCa characteristics was validated using a mTOR activator (MHY1485) and a mTOR inhibitor (Rapamycin) respectively. HIF1A siRNA was introduced to confirm the role of HIF1A. Furthermore, an in vivo nude mouse model was constructed to confirm PLAC1's influence on tumorigenesis and metastasis in CCa.

Key findings: PLAC1 upregulated hypoxia-inducible factor (HIF)-1α and Snail, promoting CCa cell proliferation, migration, and invasion via the mTOR/HIF-1α/Snail pathway. Enrichment analysis of PLAC1-associated differentially expressed genes implicated their involvement in CCa and tumor promotion. In a xenograft mouse model, PLAC1 exhibited a pro-tumorigenic effect, which can be reversed by siRNA targeting HIF1A.

Significance: This study enhances our understanding of PLAC1's role and molecular mechanisms in CCa progression, highlighting its potential as a diagnostic, prognostic, and therapeutic marker for the management of CCa.