Objective To analyze the distribution pattern of SRSF1 in endometrial cancer tissues, and explore its influence on the ability of macrophages to phagocytize apoptotic cells and its potential mechanism.

Methods Based on the GSE173682 dataset of GEO database, the cell atlas of endometrial cancer was plotted using single-cell RNA sequencing technology. An Ishikawa cell model with low expression of SRSF1 was established through lentivirus-mediated gene silencing technology. The effects of gene silencing was verified by qRT-PCR and Western blotting. The cells function was assessed by CCK-8 proliferation detection, colony formation test, migration and invasion test, etc. The AUCell algorithm was used to quantitatively evaluate the efferocytosis ability of different cell populations, and its correlation with the expression of SRSF1 was analyzed.

Results Single-cell analysis revealed that SRSF1 was mainly concentrated in the expression of cancer cells and interstitial fibroblasts in endometrial cancer tissues. After silencing SRSF1, the proliferation ability of Ishikawa cells was inhibited from 24h, and this effect persisted until 96 h (P ＜ 0.01), with the inhibitory effects being most obvious at 72 h and 96 h. The efficiency of cell colony formation decreased by approximately 65.8% (P ＜ 0.01). The migration experiment showed that the number of transmembrane cells decreased by approximately 72.1%, and the invasion ability decreased by approximately 68.3% (P ＜ 0.01). At the molecular level, the knockdown of SRSF1 led to an increase of approximately 2.3 times in the epithelial marker E-Cadherin, while the mesenchymal markers N-Cadherin and Vimentin decreased by approximately 60% and 55%, respectively (P ＜ 0.01). The functional score indicated that the cell population with high expression of SRSF1 exhibited stronger efferocytosis activity (AUC ＞ 0.073), and this expression pattern was closely related to the differentiation process of macrophages.

Conclusions Research has confirmed that SRSF1 not only directly regulates the malignant phenotype of endometrial cancer cells but may also reshape the tumor immune environment by influencing the phagocytic function of macrophages, which can provide a theoretical basis for the development of new therapeutic strategies.