Phospholipase Cε1 activates Rap1 signaling pathway to promote proliferation, EMT and angiogenesis of choriocarcinoma cells.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.