TMEM252 inhibits epithelial-mesenchymal transition and progression in papillary thyroid carcinoma by regulating Notch1 expression

Head Neck. 2025 Jan;47(1):324-338. doi: 10.1002/hed.27922. Epub 2024 Aug 16.

Abstract

Background: Papillary thyroid carcinoma (PTC) accounts for about 85% of thyroid cancer cases. Transmembrane protein 252 (TMEM252) is a gene encoding a transmembrane protein that has only been reported to be associated with triple-negative breast cancer. Herein, we first elucidated the physiological roles and possible regulatory proteins of TMEM252 in PTC pathogenesis.

Methods: Quantitative real-time polymerase chain reaction, western blot, and immunohistochemical analyses were utilized to ascertain the relative TMEM252 expression in PTC and surrounding normal tissues. Functional investigations involved CCK-8 viability assay, EdU incorporation assay for proliferation, transwell assays for migration and invasion, and an in vivo tumor development assessment to evaluate the TMEM252-mediated regulation of tumor formation.

Results: Our results first revealed diminished TMEM252 transcript and protein expressions in PTC tissues and cell lines. TMEM252 overexpression suppressed cell proliferation through reducing p53, p21, and p16 expression. Conversely, TMEM252 depletion has opposite effects in PTC cells both in vivo. Additionally, the upregulation of TMEM252 demonstrated cell migration and invasion suppression by impeding the epithelial-mesenchymal transition (EMT) process via inhibition of the Notch pathway. Furthermore, overexpression of TMEM252 suppressed tumor growth in vivo.

Conclusion: Our study elucidates that TMEM252 suppresses PTC progression by modulating the Notch pathway. These findings underscore TMEM252 is a potential therapeutic target in managing PTC.

Keywords: Notch; TMEM252; papillary thyroid carcinoma; prognosis; proliferation.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation* / genetics
  • Disease Progression
  • Epithelial-Mesenchymal Transition* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Receptor, Notch1* / genetics
  • Receptor, Notch1* / metabolism
  • Thyroid Cancer, Papillary* / genetics
  • Thyroid Cancer, Papillary* / metabolism
  • Thyroid Cancer, Papillary* / pathology
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / metabolism
  • Thyroid Neoplasms* / pathology

Substances

  • Receptor, Notch1
  • Membrane Proteins
  • NOTCH1 protein, human