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TESC promotes differentiated thyroid cancer development by activating ERK and weakening NIS and radioiodine uptake

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Abstract

Purpose

Most differentiated thyroid cancer (DTC) patients have a good prognosis after surgery, but radioiodine refractory differentiated thyroid cancer (RAIR-DTC) patients have a significantly reduced 5-year survival rate (<60%) and a significantly increased recurrence rate (>30%). This study aimed to clarify the tescalcin (TESC) role in promoting the malignant PTC progression and providing a potential target for RAIR-DTC treatment.

Methods

We analyzed TESC expression and clinicopathological characteristics using the Cancer Genome Atlas (TCGA) and performed qRT-PCR on tissue samples. TPC-1 and IHH-4 proliferation, migration, and invasion were detected after transfection with TESC-RNAi. Using Western blot (WB), several EMT-related indicators were detected. Moreover, iodine uptake of TPC-1 and IHH-4 after transfection with TESC-RNAi was detected. Finally, NIS, ERK1/2, and p-ERK1/2 levels were determined by WB.

Results

TESC was significantly upregulated in DTC tissues and positively correlated with BRAF V600E mutation based on data analysis from TCGA and our center. Reduced expression of TESC in both IHH-4 (BRAF V600E mutation) and TPC-1 (BRAF V600E wild type) cells significantly inhibited cell proliferation, migration, and invasion. It downregulated the EMT pathway markers Vimentin and N-cadherin, and increased E- cadherin. Moreover, TESC knockdown significantly inhibited ERK1/2 phosphorylation and decreased NIS expression in DTC cells, with a remarkably increased iodine uptake rate.

Conclusions

TESC was highly expressed in DTC tissues and may have promoted metastasis through EMT and induced iodine resistance by downregulating NIS in DTC cells.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (82103199; 22177104); Natural Science Foundation of Zhejiang Province (LY23H160024); Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (2021KY482, 2023RC001); Traditional Chinese Medicine Science and Technology Project of Zhejiang Provincial Health Commission (2023ZL240); Zhejiang Province Postdoctoral Research Excellence Funding Project (ZJ2021167); The incubation project of the First Affiliated Hospital of Wenzhou Medical University (FHY2019003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Author notes

  1. These authors contributed equally: Yawen Guo, Yefeng Cai

Authors and Affiliations

  1. Otolaryngology& Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China

    Yawen Guo, Fahuan Song, Yunye Liu, Lingling Ding, Guowan Zheng & Minghua Ge

  2. Department of Public Health, Zhejiang University School of Medicine, Hangzhou, 310014, China

    Yawen Guo & Fahuan Song

  3. Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou, 310014, China

    Yawen Guo, Fahuan Song, Guowan Zheng & Minghua Ge

  4. Clinical Research Center for Cancer of Zhejiang Province, Hangzhou, Zhejiang, 310014, China

    Yawen Guo, Fahuan Song, Guowan Zheng & Minghua Ge

  5. Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China

    Yefeng Cai

  6. Second Clinical Medical College, Zhejiang Chinese Medical University, Zhejiang Province, Hangzhou, 310053, China

    Yefeng Cai & Yiqun Hu

  7. Department of Thyroid Surgery, The Fifth Hospital Affiliated to Wenzhou Medical University, Lishui Central Hospital, Zhejiang Province, Lishui, 323000, China

    Lei Zhu

  8. Bengbu Medical College, Bengbu, Anhui, 233030, China

    Wenli Ma

  9. Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, China

    Jingyan Ge & Qian Zeng

  10. School of Information Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, China

    Lebao Li

Authors
  1. Yawen Guo
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Contributions

M.G. and G.Z. conceived and designed the experiments; Y.G. and Y.C. performed the searching and collected the data; F.S., L.Z., Y.H., Y.L., W.M., Q.Z., L.D., L.L. performed the experiment and analyzed the data; Y.G., J.G. interpretated that results and drafted the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding authors

Correspondence to Guowan Zheng or Minghua Ge.

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Conflict of interest

The authors declare no competing interests.

Ethics approval and consent to participate

This study was approved by the Ethical Committee of Zhejiang Provincial People’s Hospital (Approval No. 2019KY298), Informed consent was obtained from all individual participants included in the study.

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Guo, Y., Cai, Y., Song, F. et al. TESC promotes differentiated thyroid cancer development by activating ERK and weakening NIS and radioiodine uptake. Endocrine 81, 503–512 (2023). https://doi.org/10.1007/s12020-023-03350-6

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  • DOI: https://doi.org/10.1007/s12020-023-03350-6

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