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

Sep 23, 2026

NAC1, a transcription regulator linked to cancer, is highly expressed across multiple tumor types, including ovarian cancer, but its role in carcinogenesis is not fully defined. Prior findings showed NAC1 knockdown in ovarian clear cell carcinoma cells induces apoptosis and restores chemotherapy sensitivity. This study identified mechanisms by which NAC1 participates in endometriosis-related ovarian neoplasms, focusing on its regulatory relationship with ACOX2 through promoter binding, reporter assays, and ChIP analyses, revealing a transcriptional repression model.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Introduction

Results

NAC1 and ACOX2 expression relationship

Prognostic impact of NAC1/ACOX2

NAC1 regulation of ACOX2 promoter via CATG site

In vivo binding confirmed by ChIP

Discussion

Article NAC1/ACOX2 Axis as a Novel Therapeutic Target for Endometriosis-Related Ovarian Neoplasms Shahataj Begum Sonia 1, Kentaro Nakayama 2, *, Sultana Razia 3, Naomi Nakayama 4, Masako Ishikawa 1, Hitomi Yamashita 1, Kosuke Kanno 1, Haruo Takeshita 3, Umme Farzana Zahan 1, Hasibul Islam Sohel 1 and Satoru Kyo 1, * Academic Editor: Kuo-Hu Chen Received: 10 March 2025 Revised: 30 April 2025 Accepted: 15 May 2025 Published: 21 May 2025 Citation: Sonia, S.B.; Nakayama, K.; Razia, S.; Nakayama, N.; Ishikawa, M.; Yamashita, H.; Kanno, K.; Takeshita, H.; Zahan, U.F.; Sohel, H.I.; et al. NAC1/ACOX2 Axis as a Novel Therapeutic Target for Endometriosis-Related Ovarian Neoplasms. Int. J. Mol. Sci. 2025, 26, 4938. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms26104938 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . 1 Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, Izumo 693-8501, Japan; [sbsonia1995@gmail.com](sbsonia1995@gmail.com) (S.B.S.); [m-ishi@med.shimane-u.ac.jp](m-ishi@med.shimane-u.ac.jp) (M.I.); [meme1103@med.shimane-u.ac.jp](meme1103@med.shimane-u.ac.jp) (H.Y.); [kanno39@med.shimane-u.ac.jp](kanno39@med.shimane-u.ac.jp) (K.K.); [farzanashormi99@gmail.com](farzanashormi99@gmail.com) (U.F.Z.); [hasibulsohel1167@gmail.com](hasibulsohel1167@gmail.com) (H.I.S.) 2 Department of Obstetrics and Gynecology, Nagoya City University East Medical Center, Nagoya 464-8547, Japan 3 Department of Legal Medicine, Shimane University Faculty of Medicine, 89-1, Enya-Cho, Izumo 693-8501, Japan; [raeedahmed@yahoo.com](raeedahmed@yahoo.com) (S.R.); [htakeshi@med.shimane-u.ac.jp](htakeshi@med.shimane-u.ac.jp) (H.T.) 4 Department of General Internal Medicine, Nagoya City University East Medical Center, Nagoya 464-8547, Japan; [kennaonatsuno@yahoo.co.jp](kennaonatsuno@yahoo.co.jp) * Correspondence: [kn88@med.nagoya-cu.ac.jp](kn88@med.nagoya-cu.ac.jp) (K.N.); [satoruky@med.shimane-u.ac.jp](satoruky@med.shimane-u.ac.jp) (S.K.) Abstract: 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. Keywords: NAC1; ACOX2; ovari

FAQs

What was the main goal of this study?

To identify the molecular pathways through which NAC1 contributes to endometriosis-related ovarian neoplasms, with emphasis on its regulation of ACOX2.

How did the study examine the relationship between NAC1 and ACOX2?

It used immunohistochemistry in tumor specimens, reporter assays to test NAC1 interaction with cis-elements on the ACOX2 promoter, and ChIP assays to confirm in vivo promoter binding.

What do the findings suggest about the NAC1/ACOX2 axis?

They indicate NAC1 acts as a transcriptional repressor of ACOX2 via a proximal CATG site, and high NAC1/low ACOX2 expression is associated with worse patient survival outcomes.

Sep 23, 2026

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