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Overexpression of FHL1 suppresses papillary thyroid cancer proliferation and progression via inhibiting Wnt/β-catenin pathway

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Abstract

Purpose

The four and a half LIM domain protein 1 (FHL1) has been found to act as a tumor suppressor in several cancers. However, the clinical and functional significance, as well as underlying molecular mechanisms of FHL1 in papillary thyroid cancer (PTC) are largely unknown.

Methods

Bioinformatics analyses, qRT-PCR and Western blotting were used to investigate the expression of FHL1 in PTC. Cell proliferation was measured using CCK8, Edu, colony formation, and flow cytometry assays. Cell migration and invasion were examined by wound healing and Transwell assays. qRT-PCR, Western blot, immunofluorescence and Top/Fop reporter assays were performed to assess the underlying mechanisms.

Results

FHL1 expression was significantly downregulated in PTC. FHL1 downregulation negatively correlated with stage, T classification, and N classification of the patients. The downregulation of FHL1 is associated with poor prognosis. Overexpression of FHL1 inhibited PTC cells’ proliferation, invasion, migration and Wnt/β-catenin pathway activity. LiCl partially restored the inhibitory effects of FHL1 on aggressive phenotypes and Wnt/β-catenin pathway activity of PTC cells.

Conclusion

FHL1 is downregulated in PTC and its expression is associated with better clinical outcomes for patients with the disease. FHL1 acts as a tumor suppressor via, at least partially, suppressing Wnt/β-catenin pathway.

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Data availability

The analyzed data sets generated during the study are available from the corresponding author upon reasonable request.

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Funding

The funding for this project was provided by the National Natural Science Foundation of China (No. 82073050 and No. 82201551); Guangdong Basic and Applied Basic Research Foundation (No. 2019A1515012046 and No. 2019A1515010275); Guangzhou Technology Project (No. 202102080311).

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Authors and Affiliations

  1. Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Junxin Chen, Chuimian Zeng, Jiewen Jin, Pengyuan Zhang, Yilin Zhang, Hanrong Zhang, Yanbing Li & Hongyu Guan

  2. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China

    Chuimian Zeng & Yilin Zhang

Authors
  1. Junxin Chen
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  2. Chuimian Zeng
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  3. Jiewen Jin
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  4. Pengyuan Zhang
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  5. Yilin Zhang
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  6. Hanrong Zhang
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  7. Yanbing Li
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  8. Hongyu Guan
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Contributions

G.H.Y. and L.Y.B. contributed to the conception and the design of the work. J.J.W. and Z.P.Y. offered administrative support. Z.Y.L. and Z.H.R. provided materials for the study. C.J.X., Z.C.M. and Z.Y.L. contributed to implementation of the experiment and analysis of data. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yanbing Li or Hongyu Guan.

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Ethical approval was obtained from the Institutional Research Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University. The samples were obtained with informed consent from all patients.

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Chen, J., Zeng, C., Jin, J. et al. Overexpression of FHL1 suppresses papillary thyroid cancer proliferation and progression via inhibiting Wnt/β-catenin pathway. Endocrine (2024). https://doi.org/10.1007/s12020-023-03675-2

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