OLFML2A mediates cell cycle regulation in triple-negative breast cancer via EZH2.

Background: Triple-negative breast cancer (TNBC) is recognized as one of the most aggressive and prognostically adverse subtypes of breast cancer. The lack of effective therapeutic targets presents substantial challenges, including impediments in early diagnosis, restricted treatment options, and a pronounced tendency for drug resistance. Despite recent advancements in the diagnosis and management of TNBC, the overall survival rate for patients remains suboptimal. Consequently, gaining a more profound understanding of its biological mechanisms and developing novel therapeutic strategies are imperative scientific priorities in this domain. Methods: OLFML2A was identified as a potential therapeutic target in TNBC through analyses of the Human Protein Atlas and Kaplan-Meier databases. Its functional role was investigated using OLFML2A knockout (KO) and overexpression (OE) models in MDA-MB-231 cells. Effects on proliferation, cell cycle, and apoptosis were assessed by EdU assays, flow cytometry, RT-qPCR, western blotting, and immunofluorescence. Tumor growth and body weight were monitored Results: OLFML2A acts as an oncogenic gene in triple-negative breast cancer. The silencing of OLFML2A markedly reduced the proliferation of MDA-MB-231 cells, induced cell cycle arrest at the G1 phase, and inhibited tumor growth. In contrast, overexpression of OLFML2A reversed these effects. Comprehensive proteomic and molecular biology analyses further indicated that OLFML2A may play a role in cell cycle regulation through the modulation of EZH2. Conclusions: Our findings suggest that OLFML2A may facilitate cell cycle progression by regulating EZH2, implicating it as a potential therapeutic target for triple-negative breast cancer.