Abnormal activation of the Wnt3a/β-catenin signaling pathway promotes the expression of T-box transcription factor 3(TBX3) and the epithelial-mesenchymal transition pathway to mediate the occurrence of adenomyosis

Background T-box transcription factor 3(TBX3) is a transcription factor that can regulate cell proliferation, apoptosis, invasion, and migration in different tumor cells; however, its role in adenomyosis (ADM) has not been previously studied. Some of ADM’s pathophysiological characteristics are similar to those of malignant tumors (e.g., abnormal proliferation, migration, and invasion).

and results We hypothesized that TBX3 might have a role in ADM. We used tamoxifen-induced Institute of Cancer research (ICR) mice to establish ADM disease model. The study procedure included western blotting and immunohistochemistry to analyze protein levels; additionally, we used intraperitoneal injection of Wnt/β-catenin pathway inhibitor XAV-939 to study the relationship between TBX3 and Wnt/β-catenin pathway as well as Anti-proliferation cell nuclear antigen( PCNA) and TUNEL to detect cell proliferation and apoptosis, respectively. TBX3 overexpression and epithelial-to-mesenchymal transition (EMT) in ADM mice was found to be associated with activation of the Wnt3a/β-catenin pathway. Treatment with XAV-939 in ADM mice led to the inhibition of both TBX3 and EMT; moreover, abnormal cell proliferation was suppressed, the depth of invasion of endometrium cells was limited. Thus, the use of XAV-939 effectively inhibited further invasion of endometrial cells.

These findings suggest that TBX3 may play an important role in the development of ADM. The expression of TBX3 in ADM was regulated by the Wnt3a/β-catenin pathway. The activation of the Wnt3a/β-catenin pathway in ADM promoted TBX3 expression and induced the occurrence of EMT, thus promoting cell proliferation and inhibiting apoptosis, ultimately accelerating the development of ADM. The study provides a reference for the diagnosis of ADM. Similar content being viewed by others Data availability All data generated or analyzed during this study are included in this published article. Abbreviations - ADM: - Adenomyosis - BCA: - Bicinchoninic acid - DMSO: - Dimethyl sulfoxide - ECL: - Enhanced chemiluminescence - EMT: - Epithelial-to-mesenchymal transition - GAPDH: - Glyceraldehyde-3-phosphate dehydrogenase - H&E: - Hematoxylin and eosin - ICR: - Institute of cancer research - IHC: - Immunohistochemistry - IOD: - Integrated optical density - MOD: - Mean optical density - PBS: - Phosphate buffered saline - PCNA: - Anti-proliferation cell nuclear antigen - PMSF: - Phenylmethanesulfonyl fluoride - PVDF: - Polyvinylidene fluoride - RIPA: - Radio immunoprecipitation assay - TAM: - Tamoxifen citrate - TBX3: - T-box transcription factor 3 - α-SMA: - α-Smooth muscle actin

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The authors would like to thank the Laboratory Animal Center of Jinan University for caring for the animals in the present study. The authors would also like to thank the Central Laboratory of the School of Medicine for providing the experimental platform. Funding The present study was supported by the Guangdong Provincial Hospital of Chinese Medicine—Weixian Li famous doctor studio (Grant No. E43719) and National Famous Traditional Chinese Medicine Expert inheritance Studio—Jianling Huang (Project No. 0102016205). Author information Authors and Affiliations Contributions WQC and QZR conceived and designed the study and revised the manuscript. MQL and TL performed the experiments and wrote the manuscript. TTJ, YC, and SMY analyzed the data. LC and QHL provided clinical guidance. TTL provided guidance in HE experiments. All authors read and approved the final manuscript. Corresponding authors Ethics declarations Competing interest The authors declare that they have no competing interests. Ethical approval All animal experiments were approved by the Laboratory Animal Review Committee of Jinan University (ethics approval number, IACUC-20200905-01). Consent for publication Not applicable. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Li, M., Li, T., Jin, T. et al. Abnormal activation of the Wnt3a/β-catenin signaling pathway promotes the expression of T-box transcription factor 3(TBX3) and the epithelial-mesenchymal transition pathway to mediate the occurrence of adenomyosis. Mol Biol Rep 50, 9935–9950 (2023). https://doi.org/10.1007/s11033-023-08870-y Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s11033-023-08870-y