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

IF 5.2 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Life sciences Pub Date : 2024-11-14 DOI:10.1016/j.lfs.2024.123242
Rujun Chen, Yue Hou, Jina Chen, Fuyun Dong, Xiaoqin Wang, Junhua Guan, Liwen Zhang, He Fei, Lina Yang
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Abstract

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.

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PLAC1 通过 mTOR/HIF-1α/snail 信号通路增强宫颈癌的恶性表型。
目的:本研究探讨了胎盘特异性蛋白1(PLAC1)在宫颈癌(CCa)中的分子机制,旨在通过体外和体内实验阐明其在肿瘤发生中的作用:建立了过表达或沉默 PLAC1 的 CCa 细胞系,以评估其对细胞周期、细胞凋亡和 PLAC1/mTOR/HIF-1α/Snail 信号通路中关键蛋白表达的影响。进行了功能测定,以评估 PLAC1/mTOR/HIF-1α/Snail 调节通路对细胞增殖、迁移和侵袭的影响。分别使用mTOR激活剂(MHY1485)和mTOR抑制剂(雷帕霉素)验证了mTOR信号通路在PLAC1介导的CCa特性调节中的作用。引入 HIF1A siRNA 以证实 HIF1A 的作用。此外,还构建了体内裸鼠模型,以证实PLAC1对CCa肿瘤发生和转移的影响:PLAC1上调缺氧诱导因子(HIF)-1α和蜗牛,通过mTOR/HIF-1α/蜗牛通路促进CCa细胞增殖、迁移和侵袭。对与 PLAC1 相关的差异表达基因进行的富集分析表明,这些基因参与了 CCa 和肿瘤的促进过程。在异种移植小鼠模型中,PLAC1表现出了促肿瘤作用,而这种作用可以通过靶向HIF1A的siRNA逆转:这项研究加深了我们对PLAC1在CCa进展中的作用和分子机制的理解,凸显了其作为CCa诊断、预后和治疗标志物的潜力。
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来源期刊
Life sciences
Life sciences 医学-药学
CiteScore
12.20
自引率
1.60%
发文量
841
审稿时长
6 months
期刊介绍: Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.
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