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HIF-1α contributes to metastasis in choriocarcinoma by regulating DEC1 expression

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Abstract

Purpose

To elucidate the underlying mechanism of HIF-1α in migration and invasion of choriocarcinoma.

Methods

Cell proliferation was determined by CCK-8 assay when cell invasion was detected by transwell assay. The protein expression was detected by western blotting, immunohistochemistry, and qPCR assay.

Result

HIF-1α was shown to be strongly expressed in both clinical tumour tissues and cell lines in choriocarcinoma. When HIF-1α was efficiently knocked down in JEG3 cells, the proliferation rate was reduced by approximately 50% and the number of cells that migrated through the transwell insert was greatly decreased. The cell invasion rate was also significantly reduced. Moreover, typical markers of epithelial–mesenchymal transition such as E-cadherin, were increased, while vimentin and α–SMA were decreased after HIF-1α knockdown. In contrast, overexpression of DEC1 reversed the effects of HIF-1α knockdown. Cell proliferation, migration, and invasion were partially recovered. The level of E-cadherin was decreased, while the level of vimentin and α–SMA was increased. In addition, the level of β-catenin and LEF1 was downregulated after HIF-1α knockdown. The expression of MMP2 and MMP9 also declined. However, overexpression of DEC1 after HIF-1α knockdown partially reversed the expression pattern of these molecules.

Conclusion

HIF-1α contributed to EMT and metastasis through activation of canonical β-catenin signalling in choriocarcinoma and this process was dependent on DEC1. This study provides a new mechanism of HIF-1α in choriocarcinoma and suggests that intervention with DEC1 might be a promising therapeutic choice for choriocarcinoma.

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Availability of data and materials

The data in this paper could be available at reasonable request.

References

  1. Rashid M, Zadeh LR, Baradaran B, Molavi O, Ghesmati Z, Sabzichi M, et al. Up-down regulation of HIF-1α in cancer progression. Gene. 2021;798: 145796.

    Article  CAS  PubMed  Google Scholar 

  2. Yu Q, Dong L, Li Y, Liu GW. SIRT1 and HIF-1α signaling in metabolism and immune responses. Cancer Lett. 2018;418:20–6.

    Article  CAS  PubMed  Google Scholar 

  3. Li HY, Jia YF, Wang YS. Targeting HIF-1α signaling pathway for gastric cancer treatment. Pharmazie. 2019;74(1):3–7.

    CAS  PubMed  Google Scholar 

  4. Ryu N, Ogawa M, Matsui H, Usui H, Shozu M. The clinical characteristics and early detection of postpartum choriocarcinoma. Int J Gynecol Cancer. 2015;25(5):926–30.

    Article  PubMed  Google Scholar 

  5. Ferrera KP, Servin MAH, Guerrero AIH. Primary gastric choriocarcinoma. Rev Esp Enferm Dig. 2020;112(3):241.

    Google Scholar 

  6. Wreczycka-Cegielny P, Cegielny T, Oplawski M, Sawichi W, Kojs Z. Current treatment options for advanced choriocarcinoma on the basis of own case and review of the literature. Ginekol Pol. 2018;89(12):711–5.

    Article  PubMed  Google Scholar 

  7. Zhang Y, Zhao HJ, Xia XR, Diao FY, Ma X, Wang J, et al. Hypoxia-induced and HIF-1α-VEGF-mediated tight junction dysfunction in choriocarcinoma cells: Implications for preeclampsia. Clin Chim Acta. 2019;489:203–11.

    Article  CAS  PubMed  Google Scholar 

  8. Tian Q, Xue Y, Zheng W, Sun R, Ji W, Wang XY, et al. Overexpression of hypoxia-inducible factor 1α induces migration and invasion through Notch signaling. Int J Oncol. 2015;47(2):728–38.

    Article  CAS  PubMed  Google Scholar 

  9. Chen Y, Zhao BJ, Zhu Y, Zhao HQ, Ma C. HIF-1-VEGF-Notch mediates angiogenesis in temporomandibular joint osteoarthritis. Am J Transl Res. 2019;11(5):2969–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Song XW, Tang Y, Zhu J, Tian YY, Song ZH, Hu X, et al. HIF-1α induces hypoxic apoptosis of MLO-Y4 osteocytes via JNK/caspase-3 pathway and the apoptotic-osteocyte-mediated osteoclastogenesis in vitro. Tissue Cell. 2020;67: 101402.

    Article  CAS  PubMed  Google Scholar 

  11. Jia YY, Guo YT, Jin Q, Qu HN, Qi D, Song PY, et al. A SUMOylation-dependent HIF-1α/CLDN6 negative feedback mitigates hypoxia-induced breast cancer metastasis. J Exp Clin Cancer Res. 2020;39(1):42.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hou PF, Shi PC, Jiang T, Yin H, Chu SF, Shi ML, et al. DKC1 enhances angiogenesis by promoting HIF-1α transcription and facilitates metastasis in colorectal cancer. Br J Cancer. 2020;122(5):668–79.

    Article  CAS  PubMed  Google Scholar 

  13. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–8.

    Article  CAS  PubMed  Google Scholar 

  14. Murakami K, Wu YY, Imaizumi T, Aoki Y, Liu Q, Yan X, et al. DEC1 promotes hypoxia-induced epithelial-mesenchymal transition (EMT) in human hepatocellular carcinoma cells. Biomed Res. 2017;38(4):221–7.

    Article  CAS  PubMed  Google Scholar 

  15. Xue J, Dai YF, Li GF, Lang WY, Li PH, Liu YL, et al. DEC1 directly interacts with estrogen receptor (ER) to suppress proliferation of ER-positive breast cancer cells. Biochem Biophys Res Commun. 2020;528(4):740–5.

    Article  CAS  PubMed  Google Scholar 

  16. Hu R, Wang Q, Jia YF, Zhang YC, Wu B, Tian S, et al. Hypoxia-induced DEC1 mediates trophoblast cell proliferation and migration via HIF-1α signaling pathway. Tissue Cell. 2021;73: 101616.

    Article  CAS  PubMed  Google Scholar 

  17. Ohue Y, Nishikawa H. Regulatory T (Treg) cells in cancer: Can Treg cells be a new therapeutic target? Cancer Sci. 2019;110(7):2080–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bera A, Lewis SM. Regulation of epithelial-to-mesenchymal transition by alternative translation initiation mechanisms and its implications for cancer metastasis. Int J Mol Sci. 2020;21(11):4075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mittal V. Epithelial mesenchymal transition in tumor metastasis. Annu Rev Pathol. 2018;13:395–412.

    Article  CAS  PubMed  Google Scholar 

  20. Du B, Shim JS. Targeting Epithelial-Mesenchymal Transition (EMT) to overcome drug resistance in cancer. Molecules. 2016;21(7):965.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2019;20(2):69–84.

    Article  CAS  PubMed  Google Scholar 

  22. Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15(3):178–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yuan D, Yang Z, Chen YY, Li SY, Tan BX, Yu QB. Hypoxia-induced SPOP attenuates the mobility of trophoblast cells through inhibition of the PI3K/AKT/GSK3β pathway. Cell Biol Int. 2021;45(3):599–611.

    Article  CAS  PubMed  Google Scholar 

  24. Alaseem A, Alhazzani K, Dondapati P, Alobid S, Bishayee A, Rathinavelu A, et al. Matrix metalloproteinases: a challenging paradigm of cancer management. Semin Cancer Biol. 2019;56:100–15.

    Article  CAS  PubMed  Google Scholar 

  25. Winer A, Adams S, Mignatti P. Matrix metalloproteinase inhibitors in cancer therapy: turning past failures into future successes. Mol Cancer Ther. 2018;17(6):1147–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Han LP, Sheng BW, Zeng QD, Yao W, Jiang QF. Correlation between MMP2 expression in lung cancer tissues and clinical parameters: a retrospective clinical analysis. BMC Plum Med. 2020;20(1):283.

    Article  CAS  Google Scholar 

  27. Zhao CW, Yuan GH, Jiang YM, Xu JF, Ye L, Zhan WH, et al. Capn4 contributes to tumor invasion and metastasis in gastric cancer via activation of the Wnt/β-catenin/MMP9 signalling pathways. Exp Cell Res. 2020;395(2): 112220.

    Article  CAS  PubMed  Google Scholar 

  28. Gonzalez-Avila G, Sommer B, Garcia-Hernandez AA, Ramos C. Matrix metalloproteinases’ role in tumor microenvironment. Adv Exp Med Biol. 2020;1245:97–131.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Not applicable.

Funding

This study was supported by the science and technology plan projects of Jinan Municipal under grant 202019143, the second batch of science and technology plan projects of Jinan Municipal Health Commission in 2020, and Shandong Medical and Health Science and Technology Development Fund (202202050440).

Author information

Authors and Affiliations

  1. Medical Research & Laboratory Diagnostic Center, Central Hospital Affiliated to Shandong First Medical University, 105 Jiefang Road, Jinan, 250013, China

    Yihui Xu & Min Wang

  2. Department of Acupuncture & Massage, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, China

    Bao Ren

Authors
  1. Yihui Xu
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  2. Bao Ren
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  3. Min Wang
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Contributions

MW designed the study, contributed to draft of the manuscript and reviewed the manuscript. YHX carried out the major experiments and drafted the manuscript. BR analysed the data and was responsible for the clinical data acquisition.

Corresponding author

Correspondence to Min Wang.

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Ethical approval and consent to participate

Written informed consent was obtained from all patients and all experiments were approved by the Ethics Committee of Jinan Central Hospital affiliated to Shandong First Medical University.

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Informed consent for publication was obtained from all participants.

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The authors declare that they have no financial interests to declare.

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Xu, Y., Ren, B. & Wang, M. HIF-1α contributes to metastasis in choriocarcinoma by regulating DEC1 expression. Clin Transl Oncol 25, 1641–1649 (2023). https://doi.org/10.1007/s12094-022-03055-8

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  • DOI: https://doi.org/10.1007/s12094-022-03055-8

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