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Loss of STARD13 contributes to aggressive phenotype transformation and poor prognosis in papillary thyroid carcinoma

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Abstract

Purpose

StAR Related Lipid Transfer Domain Containing 13 (STARD13) serves as a tumor suppressor and has been characterized in several types of malignancies. However, the role and the molecular mechanism of STARD13 in regulating the progression of papillary thyroid carcinoma (PTC) remain underexplored.

Methods

The gene expression and clinical information of thyroid cancer were downloaded using “TCGAbiolinks” R package. Quantitative PCR and immunohistochemical staining were conducted to detect the expression of STARD13 in clinical tumor and adjacent non-tumor samples. Wound-healing assay, Transwell assay and 3D spheroid invasion assay were performed to evaluate the migratory and invasive capacities of PTC cells. Cell proliferation ability was determined by CCK-8 assay, colony formation assay and 5-ethynyl-2’-deoxyuridine (EdU) incorporation assay. The alterations of indicated proteins were detected by Western blotting.

Results

In the present study, we found that STARD13 was significantly underexpressed in PTC, which was correlated with poor prognosis. Downregulation of STARD13 might be due to methylation of promoter region. Loss-and gain-of-function experiments demonstrated that STARD13 impeded migratory and invasive capacities of PTC cells in vitro and in vivo. In addition, we found that STARD13 regulated the morphology of PTC cells and inhibited epithelial-mesenchymal transition (EMT).

Conclusion

Our results suggest that STARD13 acts as a metastasis suppressor and might be a potential therapeutic target in PTC.

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Data availability

All GSE datasets analyzed during the current study are available in the GEO repository, http://www.ncbi.nlm.nih.gov/gds. The RNA sequencing data of TCGA-THCA dataset can be obtained from TCGA, https://cancergenome.nih.gov/. The clinical information of TCGA-THCA dataset and DNA methylation data are accessible at UCSC Xena browser, https://xena.browser.net/.

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Funding

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

    Chuimian Zeng, Hai Li, Weiwei Liang, Junxin Chen, Yilin Zhang, Hanrong Zhang, Haipeng Xiao, Yanbing Li & Hongyu Guan

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

    Chuimian Zeng & Yilin Zhang

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  1. Chuimian Zeng
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  2. Hai Li
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Contributions

G.H.Y., L.Y.B. & X.H.P. conceived, designed and supervised the research and revised the manuscript. Z.C.M. & C.J.X. performed the experiments. Z.C.M., L.H. & L.W.W. analyzed the data. Z.C.M. wrote the manuscript. Z.Y.L. took part in the animal experiments. Z.H.R. collected clinical samples. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yanbing Li or Hongyu Guan.

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The authors declare no competing interests.

Ethics approval and consent to participate

The experimental protocols of our study were performed in accordance with the Helsinki Declaration and its later amendments and approved by the Institutional Research Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University. All patients have signed written informed consent. The animal experiments in this study were approved by the Institutional Animal Care and Use Committee of Sun Yat-sen University.

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Zeng, C., Li, H., Liang, W. et al. Loss of STARD13 contributes to aggressive phenotype transformation and poor prognosis in papillary thyroid carcinoma. Endocrine 83, 127–141 (2024). https://doi.org/10.1007/s12020-023-03468-7

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  • DOI: https://doi.org/10.1007/s12020-023-03468-7

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