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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

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Abstract

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).

Methods 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.

Conclusion

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.

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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

References

  1. Barbanti C, Centini G, Lazzeri L, Habib N, Labanca L, Zupi E, Afors K, Starace AC (2021) Adenomyosis and infertility: the role of the junctional zone. Gynecol Endocrinol 37(7):577–583. https://doi.org/10.1080/09513590.2021.1878131

    Article  CAS  PubMed  Google Scholar 

  2. Bird CC, McElin TW, Manalo-Estrella P (1972) The elusive adenomyosis of the uterus–revisited. Am J Obstet Gynecol 112(5):583–593. https://doi.org/10.1016/0002-9378(72)90781-8

    Article  CAS  PubMed  Google Scholar 

  3. Chapron C, Vannuccini S, Santulli P, Abrao MS, Carmona F, Fraser IS, Gordts S, Guo SW, Just PA, Noel JC, Pistofidis G, Van den Bosch T, Petraglia F (2020) Diagnosing adenomyosis: an integrated clinical and imaging approach. Hum Reprod Update 26(3):392–411. https://doi.org/10.1093/humupd/dmz049

    Article  PubMed  Google Scholar 

  4. Antero MF, Ayhan A, Segars J, Shih I-M (2020) Pathology and pathogenesis of adenomyosis. Semin Reprod Med 38(02/03):108–118. https://doi.org/10.1055/s-0040-1718922

    Article  PubMed  PubMed Central  Google Scholar 

  5. Vercellini P, Consonni D, Dridi D, Bracco B, Frattaruolo MP, Somigliana E (2014) Uterine adenomyosis and in vitro fertilization outcome: a systematic review and meta-analysis. Hum Reprod 29(5):964–977. https://doi.org/10.1093/humrep/deu041

    Article  PubMed  Google Scholar 

  6. Harada T, Khine YM, Kaponis A, Nikellis T, Decavalas G, Taniguchi F (2016) The impact of adenomyosis on women’s fertility. Obstet Gynecol Surv 71(9):557–568. https://doi.org/10.1097/ogx.0000000000000346

    Article  PubMed  PubMed Central  Google Scholar 

  7. Gordts S, Grimbizis G, Campo R (2018) Symptoms and classification of uterine adenomyosis, including the place of hysteroscopy in diagnosis. Fertil Steril 109(3):380. https://doi.org/10.1016/j.fertnstert.2018.01.006

    Article  PubMed  Google Scholar 

  8. Tan J, Yong P, Bedaiwy MA (2019) A critical review of recent advances in the diagnosis, classification, and management of uterine adenomyosis. Curr Opin Obstet Gynecol 31(4):212–221. https://doi.org/10.1097/gco.0000000000000555

    Article  PubMed  Google Scholar 

  9. Krstic M, Kolendowski B, Cecchini MJ, Postenkalo CO, Hassan HM, Andrews O, MacMillan CD, Williams KC, Leong HS, Brackstone M, Torchia J, Chambers AF, Tuck AB (2019) Tbx3 promotes progression of pre-invasive breast cancer cells by inducing EMT and directly up-regulating slug. Journal of Pathology 248(2):191–203. https://doi.org/10.1002/path.5245

    Article  CAS  PubMed  Google Scholar 

  10. Fernando RI, Litzinger M, Trono P, Hamilton DH, Schlom J, Palena C (2010) The t-box transcription factor brachyury promotes epithelial-mesenchymal transition in human tumor cells. J Clin Invest 120(2):533–544. https://doi.org/10.1172/jci38379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tazumi S, Yabe S, Uchiyama H (2010) Paraxial t-box genes, tbx6 and tbx1, are required for cranial chondrogenesis and myogenesis. Dev Biol 346(2):170–180. https://doi.org/10.1016/j.ydbio.2010.07.028

    Article  CAS  PubMed  Google Scholar 

  12. Papaioannou VE (2014) The t-box gene family: emerging roles in development, stem cells and cancer. Development 141(20):3819–3833. https://doi.org/10.1242/dev.104471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yan Y, Su M, Song Y, Tang Y, Tian X, Rood D, Lai L (2014) Tbx1 modulates endodermal and mesodermal differentiation from mouse induced pluripotent stem cells. Stem Cells Dev 23(13):1491–1500. https://doi.org/10.1089/scd.2013.0488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Melzer MK, Schirge S, Gout J, Arnold F, Srinivasan D, Burtscher I, Allgoewer C, Mulaw M, Zengerling F, Guenes C, Lickert H, Christoffels VM, Liebau S, Wagner M, Seufferlein T, Bolenz C, Moon AM, Perkhofer L, Kleger A (2023) Tbx3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration. BMC Biol 21(1):55. https://doi.org/10.1186/s12915-023-01553-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Omar R, Cooper A, Maranyane HM, Zerbini L, Prince S (2019) Col1a2 is a tbx3 target that mediates its impact on fibrosarcoma and chondrosarcoma cell migration. Cancer Lett 459:227–239. https://doi.org/10.1016/j.canlet.2019.06.004

    Article  CAS  PubMed  Google Scholar 

  16. Krstic M, Kolendowski B, Cecchini MJ, Postenkalo CO, Hassan HM, Andrews O, MacMillan CD, Williams KC, Leong HS, Brackstone M, Torchia J, Chambers AF, Tuck AB (2019) Tbx3 promotes progression of pre-invasive breast cancer cells by inducing EMT and directly up-regulating slug. J Pathol 248(2):191–203. https://doi.org/10.1002/path.5245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sims D, Maranyane HM, Damerell V, Govender D, Isaacs AW, Peres J, Prince S (2020) The c-myc/akt1/tbx3 axis is important to target in the treatment of embryonal rhabdomyosarcoma. Cancers 12(2):501. https://doi.org/10.3390/cancers12020501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Liu L, Luo N, Guo J, Xie Y, Chen L, Cheng Z (2018) Berberine inhibits growth and inflammatory invasive phenotypes of ectopic stromal cells: Imply the possible treatment of adenomyosis. J Pharmacol Sci 137(1):5–11. https://doi.org/10.1016/j.jphs.2017.12.001

    Article  CAS  PubMed  Google Scholar 

  19. Fu M, Hu Y, Lan T, Guan K-L, Luo T, Luo M (2022) The hippo signalling pathway and its implications in human health and diseases. Signal Transduct Target Ther 7(1):376. https://doi.org/10.1038/s41392-022-01191-9

    Article  PubMed  PubMed Central  Google Scholar 

  20. Akrida I, Bravou V, Papadaki H (2022) The deadly cross-talk between hippo pathway and epithelial-mesenchymal transition (EMT) in cancer. Mol Biol Rep 49(10):10065–10076. https://doi.org/10.1007/s11033-022-07590-z

    Article  CAS  PubMed  Google Scholar 

  21. Dong L, Lyu X, Faleti OD, He ML (2019) The special sternness functions of Tbx3 in stem cells and cancer development. Semin Cancer Biol 57:105–110. https://doi.org/10.1016/j.semcancer.2018.09.010

    Article  CAS  PubMed  Google Scholar 

  22. Dong L, Lin F, Wu W, Huang W, Cai Z (2016) Transcriptional cofactor mask2 is required for yap-induced cell growth and migration in bladder cancer cell. J Cancer 7(14):2132–2138. https://doi.org/10.7150/jca.16438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ghosh N, Hossain U, Mandal A, Sil PC (2019) The Wnt signaling pathway: a potential therapeutic target against cancer. Br J Cancer 1443(1):54–74. https://doi.org/10.1111/nyas.14027

    Article  Google Scholar 

  24. Zimmerli D, Borrelli C, Jauregi-Miguel A, Soderholm S, Brutsch S, Doumpas N, Reichmuth J, Murphy-Seiler F, Aguet M, Basler K, Moor AE, Cantu C (2020) Tbx3 acts as tissue-specific component of the Wnt/beta-catenin transcriptional complex. Elife. https://doi.org/10.7554/eLife.58123

    Article  PubMed  PubMed Central  Google Scholar 

  25. Luedtke TH, Rudat C, Wojahn I, Weiss AC, Kleppa MJ, Kurz J, Farin HF, Moon A, Christoffels VM, Kispert A (2016) Tbx2 and Tbx3 act downstream of SHH to maintain canonical Wnt signaling during branching morphogenesis of the murine lung. Dev Cell 39(2):239–253. https://doi.org/10.1016/j.devcel.2016.08.007

    Article  CAS  Google Scholar 

  26. Aydogdu N, Rudat C, Trowe MO, Kaiser M, Luedtke TH, Taketo MM, Christoffels VM, Moon A, Kispert A (2018) Tbx2 and Tbx3 act downstream of canonical Wnt signaling in patterning and differentiation of the mouse ureteric mesenchyme. Development. https://doi.org/10.1242/dev.171827

    Article  PubMed  Google Scholar 

  27. Chen Y-J, Li H-Y, Huang C-H, Twu N-F, Yen M-S, Wang P-H, Chou T-Y, Liu Y-N, Chao K-C, Yang M-H (2010) Oestrogen-induced epithelial-mesenchymal transition of endometrial epithelial cells contributes to the development of adenomyosis. J Pathol 222(3):261–270. https://doi.org/10.1002/path.2761

    Article  CAS  PubMed  Google Scholar 

  28. Brabletz S, Schuhwerk H, Brabletz T, Stemmler MP (2021) Dynamic EMT: A multi-tool for tumor progression. Embo J. https://doi.org/10.15252/embj.2021108647

    Article  PubMed  PubMed Central  Google Scholar 

  29. Taki M, Abiko K, Ukita M, Murakami R, Yamanoi K, Yamaguchi K, Hamanishi J, Baba T, Matsumura N, Mandai M (2021) Tumor immune microenvironment during epithelial-mesenchymal transition. Clin Cancer Res 27(17):4669–4679. https://doi.org/10.1158/1078-0432.Ccr-20-4459

    Article  CAS  PubMed  Google Scholar 

  30. Krstic M, Hassan HM, Kolendowski B, Hague MN, Anborgh PH, Postenka CO, Torchia J, Chambers AF, Tuck AB (2020) Isoform-specific promotion of breast cancer tumorigenicity by Tbx3 involves induction of angiogenesis. Lab Invest 100(3):400–413. https://doi.org/10.1038/s41374-019-0326-6

    Article  CAS  PubMed  Google Scholar 

  31. Shen M, Liu X, Zhang H, Guo S-W (2015) Transforming growth factor β1 signaling coincides with epithelial–mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis in mice. Hum Reprod 31(2):355–369. https://doi.org/10.1093/humrep/dev314

    Article  CAS  PubMed  Google Scholar 

  32. Muskhelishvili L, Latendresse JR, Kodell RL, Henderson EB (2003) Evaluation of cell proliferation in rat tissues with brdu, pcna, ki-67(mib-5) immunohistochemistry and in situ hybridization for histone mrna. J Histochem Cytochem 51(12):1681–1688. https://doi.org/10.1177/002215540305101212

    Article  CAS  PubMed  Google Scholar 

  33. Liu D, Yang N, Liang Y, Chen M, Yang F, Liu L, Yao S (2020) Increased expression of epithelial cell adhesion molecule and its possible role in epithelial–mesenchymal transition in endometriosis. J Obstet Gynaecol Res 46(10):2066–2075. https://doi.org/10.1111/jog.14401

    Article  CAS  PubMed  Google Scholar 

  34. Zhang Z, Qi J, Fan X, Pan M (2023) Xav939 improves the prognosis of myocardial infarction by blocking the Wnt/beta-catenin signalling pathway. Appl Biochem Biotechnol. https://doi.org/10.1007/s12010-023-04485-y

    Article  PubMed  PubMed Central  Google Scholar 

  35. Huang S-MA, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, Hild M, Shi X, Wilson CJ, Mickanin C, Myer V, Fazal A, Tomlinson R, Serluca F, Shao W, Cheng H, Shultz M, Rau C, Schirle M, Schlegl J, Ghidelli S, Fawell S, Lu C, Curtis D, Kirschner MW, Lengauer C, Finan PM, Tallarico JA, Bouwmeester T, Porter JA, Bauer A, Cong F (2009) Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 461(7264):614–620. https://doi.org/10.1038/nature08356

    Article  CAS  PubMed  Google Scholar 

  36. Chen B, Dodge ME, Tang W, Lu J, Ma Z, Fan C-W, Wei S, Hao W, Kilgore J, Williams NS, Roth MG, Amatruda JF, Chen C, Lum L (2009) Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol 5(2):100–107. https://doi.org/10.1038/nchembio.137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Shetti D, Zhang B, Fan C, Mo C, Lee BH, Wei K (2019) Low dose of paclitaxel combined with xav939 attenuates metastasis, angiogenesis and growth in breast cancer by suppressing Wnt signaling. Cells 8(8):892. https://doi.org/10.3390/cells8080892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Garcia-Solares J, Donnez J, Donnez O, Dolmans MM (2018) Pathogenesis of uterine adenomyosis: invagination or metaplasia? Fertil Steril 109(3):371–379. https://doi.org/10.1016/j.fertnstert.2017.12.030

    Article  PubMed  Google Scholar 

  39. Feng X, Yao W, Zhang Z, Yuan F, Liang L, Zhou J, Liu S, Song J (2018) T-box transcription factor Tbx3 contributes to human hepatocellular carcinoma cell migration and invasion by repressing e-cadherin expression. Oncol Res 26(6):959–966. https://doi.org/10.3727/096504017x15145624664031

    Article  PubMed  PubMed Central  Google Scholar 

  40. Krstic M, Macmillan CD, Leong HS, Clifford AG, Souter LH, Dales DW, Postenka CO, Chambers AF, Tuck AB (2016) The transcriptional regulator Tbx3 promotes progression from non-invasive to invasive breast cancer. BMC Cancer 16(1):671. https://doi.org/10.1186/s12885-016-2697-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Miao Z-F, Liu X-Y, Xu H-M, Wang Z-N, Zhao T-T, Song Y-X, Xing Y-N, Huang J-Y, Zhang J-Y, Xu H, Xu Y-Y (2016) Tbx3 overexpression in human gastric cancer is correlated with advanced tumor stage and nodal status and promotes cancer cell growth and invasion. Virchows Arch 469(5):505–513. https://doi.org/10.1007/s00428-016-2007-9

    Article  CAS  PubMed  Google Scholar 

  42. Khan SF, Damerell V, Omar R, Du Toit M, Khan M, Maranyane HM, Mlaza M, Bleloch J, Bellis C, Sahm BDB, Peres J, ArulJothi KN, Prince S (2020) The roles and regulation of Tbx3 in development and disease. Gene. https://doi.org/10.1016/j.gene.2019.144223

    Article  PubMed  PubMed Central  Google Scholar 

  43. Zimmerli D, Borrelli C, Jauregi-Miguel A, Söderholm S, Brütsch S, Doumpas N, Reichmuth J, Murphy-Seiler F, Aguet M, Basler K, Moor AE, Cantù C (2020) Tbx3 acts as tissue-specific component of the Wnt/β-catenin transcriptional complex. Elife 9:e58123. https://doi.org/10.7554/eLife.58123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Oh SJ, Shin JH, Kim TH, Lee HS, Yoo JY, Ahn JY, Broaddus RR, Taketo MM, Lydon JP, Leach RE, Lessey BA, Fazleabas AT, Lim JM, Jeong J-W (2013) Β-catenin activation contributes to the pathogenesis of adenomyosis through epithelial–mesenchymal transition. J Pathol 231(2):210–222. https://doi.org/10.1002/path.4224

    Article  CAS  PubMed  Google Scholar 

  45. Zhang J, Cai H, Sun L, Zhan P, Chen M, Zhang F, Ran Y, Wan J (2018) Lgr5, a novel functional glioma stem cell marker, promotes EMT by activating the Wnt/β-catenin pathway and predicts poor survival of glioma patients. J Exp Clin Cancer Res 37(1):225. https://doi.org/10.1186/s13046-018-0864-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wu J, Li H, Shi M, Zhu Y, Ma Y, Zhong Y, Xiong C, Chen H, Peng C (2019) Tet1-mediated DNA hydroxymethylation activates inhibitors of the Wnt/β-catenin signaling pathway to suppress EMT in pancreatic tumor cells. J Exp Clin Cancer Res 38(1):348. https://doi.org/10.1186/s13046-019-1334-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zhao YR, Wang JL, Xu C, Li YM, Sun B, Yang LY (2019) Heg1 indicates poor prognosis and promotes hepatocellular carcinoma invasion, metastasis, and EMT by activating Wnt/β-catenin signaling. Clin Sci (Lond) 133(14):1645–1662. https://doi.org/10.1042/CS20190225

    Article  CAS  PubMed  Google Scholar 

  48. Tian S, Peng P, Li J, Deng H, Zhan N, Zeng Z, Dong W (2020) Serpinh1 regulates EMT and gastric cancer metastasis via the Wnt/β-catenin signaling pathway. Aging 12(4):3574–3593. https://doi.org/10.18632/aging.102831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Batlle E, Sancho E, Francí C, Domínguez D, Monfar M, Baulida J, García de Herreros A (2000) The transcription factor snail is a repressor of e-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2(2):84–89. https://doi.org/10.1038/35000034

    Article  CAS  PubMed  Google Scholar 

  50. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117(7):927–939. https://doi.org/10.1016/j.cell.2004.06.006

    Article  CAS  PubMed  Google Scholar 

  51. Sánchez-Tilló E, de Barrios O, Siles L, Cuatrecasas M, Castells A, Postigo A (2011) Β-catenin/tcf4 complex induces the epithelial-to-mesenchymal transition (EMT)-activator zeb1 to regulate tumor invasiveness. Proc Natl Acad Sci USA 108(48):19204–19209. https://doi.org/10.1073/pnas.1108977108

    Article  PubMed  PubMed Central  Google Scholar 

  52. Benagiano G, Brosens I, Habiba M (2013) Structural and molecular features of the endomyometrium in endometriosis and adenomyosis. Hum Reprod Update 20(3):386–402. https://doi.org/10.1093/humupd/dmt052

    Article  CAS  PubMed  Google Scholar 

  53. Vannuccini S, Tosti C, Carmona F, Huang SJ, Chapron C, Guo SW, Petraglia F (2017) Pathogenesis of adenomyosis: an update on molecular mechanisms. Reprod Biomed Online 35(5):592–601. https://doi.org/10.1016/j.rbmo.2017.06.016

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

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).

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Author notes

  1. Mengqi Li and Ting Li are co-first authors, they are equally important in conducting experiments and writing papers in this study.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Guangzhou, 510632, People’s Republic of China

    Mengqi Li, Ting Li, Tingting Jin, Simiao Yan & Wanqun Chen

  2. Department of Gynecology, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, People’s Republic of China

    Yi Chen, Lan Cheng, Qiheng Liang & Qingzhen Ran

  3. Division of Histology and Embryology, International Joint Laboratory for Embryonic Development & Prenatal Medicine, School of Medicine, Jinan University, Guangzhou, 510632, People’s Republic of China

    Tingting Li

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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.

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Correspondence to Qingzhen Ran or Wanqun Chen.

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All animal experiments were approved by the Laboratory Animal Review Committee of Jinan University (ethics approval number, IACUC-20200905-01).

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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

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