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FUS-Mediated CircFGFR1 Accelerates the Development of Papillary Thyroid Carcinoma by Stabilizing FGFR1 Protein

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Abstract

Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer and its incidence is rising globally. The molecular mechanisms of PTC progression remain unclear, hindering the development of effective treatments. This study focuses on hsa_circ_0008016 (circFGFR1), a circular RNA significantly up-regulated in PTC cells. Silencing circFGFR1 inhibited PTC cell proliferation and increased cell apoptosis, suggesting its role in PTC progression. The RNA-binding protein FUS was identified as a promoter of circFGFR1 formation. While circFGFR1 does not influence FGFR1 mRNA translation, it inhibits ubiquitination and degradation of FGFR1 protein, prolonging its half-life. CircFGFR1 also interacts with protein CBL, inhibiting CBL-mediated ubiquitination of FGFR1 proteins. Rescue assays confirmed circFGFR1 promotes PTC cell growth through mediating FGFR1. This study highlights the potential of circFGFR1 as a therapeutic target, offering insights into PTC’s molecular mechanisms, and paving the way for novel treatment strategies.

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Data Availability

Data are available on request from the authors.

Abbreviations

EdU:

5-ethynyl-20-deoxyuridine

AGE:

Agarose gel electrophoresis

ATCC:

American Type Culture Collection

CCK-8:

Cell counting kit 8

CircRNAs:

Circular RNAs

Co-IP:

Co-Immunoprecipitation

cDNA:

Complementary DNA

FGFR:

Fibroblast growth factor receptor

GST:

Glutathione-S-transferase

PTC:

Papillary thyroid cancer

RBPs:

RNA binding proteins

SDS-PAGE:

Sodium dodecyl sulfate–polyacrylamide gel electrophoresis

TC:

Thyroid cancer

TUNEL:

Transferase-mediated dUTP nick-end labeling

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Acknowledgements

Heartfelt thanks to all the team members for their hard work.

Funding

This work was supported by the [National Natural Science Foundation of China] under Grant (No. 82200225); [Research Project of Young Scholars of Breast Cancer in China – Wu Jieping Foundation] under Grant (No. 320.6750.2021-10-25); [Research Fund of Anhui Medical University] under Grant (No. 2018xkj038); [Key Project of Higher Education Humanities and Social Sciences of Anhui Province] under Grant (No. SK2021A0167).

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Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, 230022, China

    Lu Zheng & Benzhong Wang

  2. Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, Anhui, 230601, China

    Lu Zheng, Tong Tang, Chenyu Sun, Xiao Chen & Wanwan Li

  3. Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, Anhui, 230601, China

    Zhitao Wang

Authors
  1. Lu Zheng
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  2. Tong Tang
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  3. Zhitao Wang
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  4. Chenyu Sun
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  5. Xiao Chen
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  6. Wanwan Li
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  7. Benzhong Wang
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Contributions

Conceptualization: LZ. Data Curation: TT, ZW, CS and XC. Formal Analysis: TT, ZW, CS and XC. Funding Acquisition: BW. Investigation: LZ. Methodology: LZ. Project Administration: LZ. Resources: BW. Software: WL. Supervision: LZ. Validation: LZ. Visualization: LZ. Writing – Original Draft Preparation: BW. Writing – Review & Editing: BW.

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Correspondence to Benzhong Wang.

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Zheng, L., Tang, T., Wang, Z. et al. FUS-Mediated CircFGFR1 Accelerates the Development of Papillary Thyroid Carcinoma by Stabilizing FGFR1 Protein. Biochem Genet (2024). https://doi.org/10.1007/s10528-023-10630-3

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  • DOI: https://doi.org/10.1007/s10528-023-10630-3

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