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

Autor: Chen R; Department of Gynecology and Obstetrics, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, PR China., Hou Y; Department of Gynecology and Obstetrics, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, PR China; Central Laboratory, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, PR China., Chen J; Department of Gynecology and Obstetrics, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, PR China., Dong F; Department of Gynecology and Obstetrics, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, PR China., Wang X; Department of Gynecology and Obstetrics, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, PR China., Guan J; Department of Gynecology and Obstetrics, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, PR China., Zhang L; Department of Gynecology and Obstetrics, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, PR China., Fei H; Department of Gynecology and Obstetrics, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, PR China. Electronic address: feihe@5thhospital.com., Yang L; Department of Gynecology and Obstetrics, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, PR China; Central Laboratory, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, PR China. Electronic address: linayang12@fudan.edu.cn.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2024 Dec 15; Vol. 359, pp. 123242. Date of Electronic Publication: 2024 Nov 15.
DOI: 10.1016/j.lfs.2024.123242
Abstrakt: 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 mTOR activator MHY1485 and 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 promoted proliferation, migration, and invasion via the mTOR/HIF-1α/Snail pathway in CCa cells. Enrichment analysis of PLAC1-associated differentially expressed genes further 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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