Introduction Endometrial cancer (EC) is a common female reproductive system malignant tumor, with increasing incidence rates and poor prognosis in recurrent/metastatic cases. The interaction between long non-coding RNA HOTAIR and polycomb repressive complex 2 (PRC2) causes the abnormal suppression of tumor suppressors, which plays a crucial role in tumor development. This study aims to investigate the potential of AC1Q3QWB (AQB) to interrupt the HOTAIR-EZH2 interaction in EC and evaluate a novel combination therapy of AQB and tazemetostat (TAZ).

Methods RNA immunoprecipitation (RIP) and chromatin isolation by RNA purification (ChIRP) assays were utilized to verify the interference of AQB with HOTAIR-EZH2 interaction in EC cells. The Agilent Human ceRNA Microarray was employed to identify tumor suppressors upregulated by AQB and TAZ, while the chromatin immunoprecipitation (ChIP) assay was performed to investigate the mechanism of genes activation. The combination therapy of AQB and TMZ was used for in vivo experiments.

Results AQB inhibited HOTAIR and EZH2 binding in EC cells, restoring the expression of numerous tumor suppressors. In vitro, the combination of AQB and TAZ produced a synergistic effect, significantly upregulating CDKN1A and SOX17, which resulted in cell cycle arrest and inhibited the proliferation, migration and invasion of EC cells. Additionally, it showed that AQB can enhance the anti-tumor effect of TAZ in vivo.

Conclusion/Implications AQB has demonstrated a promising inhibitory effect on EC cells. When combined with TAZ, the expression of CDKN1A and SOX17 was significantly upregulated, resulting in more potent anti-tumor effects. This combination therapy could provide a novel strategy for treating EC.