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

Endocrine. 2024 Jan;83(1):127-141. doi: 10.1007/s12020-023-03468-7. Epub 2023 Aug 4.

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.

Keywords: Epithelial-mesenchymal transition; Invasion; Migration; Papillary thyroid carcinoma; STARD13.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Prognosis
  • Thyroid Cancer, Papillary / pathology
  • Thyroid Neoplasms* / pathology
  • Tumor Suppressor Proteins / genetics

Substances

  • MicroRNAs
  • STARD13 protein, human
  • GTPase-Activating Proteins
  • Tumor Suppressor Proteins