NAC1/ACOX2 Axis as a Novel Therapeutic Target for Endometriosis-Related Ovarian Neoplasms

NAC1, a transcription regulator protein associated with cancer, is highly expressed in several tumor types, including ovarian cancer. However, it remains unclear how NAC1 is involved in carcinogenesis. Our previous studies demonstrated that the knockdown of NAC1 in ovarian clear cell carcinoma (OCCC) cell lines induces apoptosis and restores their sensitivity to chemotherapy, suggesting NAC1 as a potential therapeutic target. The present study aimed to identify molecular pathways through which NAC1 is involved in the development of endometriosis-related ovarian neoplasms (ERONs). Immunohistochemistry was performed to clarify the relationship between NAC1 and the potential target protein ACOX2 in surgical specimens of ERONs. Reporter assays were conducted to determine the interaction of NAC1 with the specific cis-element on the ACOX2 promoter. Subsequently, a ChIP assay was performed to investigate the in vivo interaction of NAC1 with the ACOX2 promoter. There was an inverse relationship between NAC1 and ACOX2 expressions in the tumor specimens of ERONs. High NAC1/low ACOX2 expression was found to be a worse prognostic marker for patient survival. Reporter assays demonstrated that NAC1 negatively regulated the ACOX2 promoter via the proximal CATG site. ChIP assays confirmed in vivo binding of NAC1 to the promoter. The present study implicated that NAC1 may contribute to the development of ERONs as a transcriptional repressor by regulating ACOX2 expression via specific binding sites on the promoter, providing a novel insight into the NAC1/ACOX2 axis as a potential therapeutic target of this tumor type.