Wang Dongjie, Liu Chunmeng, Tian Cha, Fang Junfeng, Ye Kefan
Department of Gynaecology, Yunnan Province Clinical Research Center for Gynecological and Obstetric Disease, The First People's Hospital of Yunnan Province, No. 157, Jinbi Road, Xishan District, Kunming, 650032, Yunnan, China.
The Affiliated Hospital of Kunming University of Science and Technology, No. 157, Jinbi Road, Xishan District, Kunming, 650032, Yunnan, China.
Mol Biol Rep. 2025 Aug 4;52(1):790. doi: 10.1007/s11033-025-10884-7.
Choriocarcinoma is a rare yet highly malignant gestational trophoblastic tumor, and its molecular mechanisms remain largely unclear. This study reveals the critical role of phospholipase Cε1 (PLCE1) in the malignant progression of choriocarcinoma and its epigenetic regulatory mechanisms.
The GSE88873 dataset was analyzed to assess PLCE1 expression in choriocarcinoma. PLCE1 expression was then quantified in choriocarcinoma tissues and cell lines (JAR and BEWO) versus normal trophoblastic controls using RT-qPCR and Western blot analysis. Functional verification assays were performed via PLCE1 knockdown in choriocarcinoma cell lines.
Analysis of GSE88873 demonstrated significant overexpression of PLCE1 in choriocarcinoma cell lines, with pan-cancer analysis showing its widespread upregulation in various tumors. Both mRNA and protein expression levels of PLCE1 were markedly elevated in choriocarcinoma tissues and cell lines compared to normal trophoblastic tissues and cells. PLCE1 knockdown suppressed choriocarcinoma cell proliferation, induced apoptosis, and reversed epithelial-mesenchymal transition (EMT). Notably, PLCE1 silencing significantly impaired the tube-forming capacity of vascular endothelial cells induced by choriocarcinoma-conditioned medium. Mechanistic investigations further demonstrated that PLCE1 mRNA contains abundant m6A modification sites, with methyltransferase METTL14 enhancing its stability through m6A modification. Additionally, PLCE1 activates the Rap1 signaling pathway to promote downstream VEGF secretion, and Rap1 activation reverses the PLCE1 knockdown-induced suppression of cell proliferation, EMT blockade, and diminished angiogenic capacity.
In summary, this study is the first to elucidate that PLCE1 maintains high expression via METTL14-mediated m6A methylation, subsequently driving choriocarcinoma cell proliferation, EMT, and angiogenesis through activation of the Rap1/VEGF axis.
绒毛膜癌是一种罕见但高度恶性的妊娠滋养细胞肿瘤，其分子机制在很大程度上仍不清楚。本研究揭示了磷脂酶Cε1（PLCE1）在绒毛膜癌恶性进展中的关键作用及其表观遗传调控机制。
分析GSE88873数据集以评估PLCE1在绒毛膜癌中的表达。然后使用RT-qPCR和蛋白质印迹分析对绒毛膜癌组织和细胞系（JAR和BEWO）与正常滋养细胞对照中的PLCE1表达进行定量。通过在绒毛膜癌细胞系中敲低PLCE1进行功能验证试验。
对GSE88873的分析表明PLCE1在绒毛膜癌细胞系中显著过表达，泛癌分析显示其在各种肿瘤中广泛上调。与正常滋养组织和细胞相比，绒毛膜癌组织和细胞系中PLCE1的mRNA和蛋白质表达水平均明显升高。敲低PLCE1可抑制绒毛膜癌细胞增殖、诱导凋亡并逆转上皮-间质转化（EMT）。值得注意的是，PLCE1沉默显著损害了绒毛膜癌条件培养基诱导的血管内皮细胞的成管能力。机制研究进一步表明，PLCE1 mRNA含有丰富的m6A修饰位点，甲基转移酶METTL14通过m6A修饰增强其稳定性。此外，PLCE1激活Rap1信号通路以促进下游VEGF分泌，并且Rap1激活可逆转PLCE1敲低诱导的细胞增殖抑制、EMT阻断和血管生成能力减弱。
总之，本研究首次阐明PLCE1通过METTL14介导的m6A甲基化维持高表达，随后通过激活Rap1/VEGF轴驱动绒毛膜癌细胞增殖、EMT和血管生成。
