80MAP17 promotes the tumorigenesis of papillary thyroid carcinoma by reducing the stability of p53

Front Biosci (Landmark Ed). 2021 Oct 30;26(10):777-788. doi: 10.52586/4987.

Abstract

Background: Papillary thyroid cancer (PTC) is an endocrine malignancy whose incidence has increased rapidly worldwide. MAP17 (PDZKIP1) is a small protein related to tumor progression. The aim of this study was to investigate the role of MAP17 in PTC and the underlying molecular mechanism. Methods: Bioinformatics, Western blotting and immunohistochemistry were used to analyze the expression of MAP17 in PTC. The gene transcription was measured by qPCR. Cell viability was determined by CCK8 assay. Cell growth was measured by clonal formation assay. Cell apoptosis was measured by TUNEL. Wound healing assay and transwell assay were used to measure the mobility of cells. The expression of E-cadherin and N-cadherin was determined by immunofluorescence. The effect of MAP17 on tumor growth was determined in animal experiments. Results: The results showed that MAP17 was up-regulated in PTC, which significantly promoted the growth and motility of PTC cells, but inhibited cell apoptosis. Besides, overexpression of MAP17 accelerated cycloheximide (CHX, a protein synthesis inhibitor)-induced p53 degradation, while low expression of MAP17 slowed down CHX-induced p53 degradation, suggesting that MAP17 can regulate p53 stability. Notably, NUMB exhibited an opposite effect on P53 stability. Interestingly, p53 overexpression reversed the effects of MAP17 overexpression on cell viability, motility, and apoptosis, indicating that p53 was involved in the progression of PTC. In vivo studies have shown that tumor growth was positively correlated with MAP17 expression and negatively correlated with p53 expression. Conclusion: Our findings revealed that MAP17 exhibited carcinogenic effects through interacting with NUMB to reduce the stability of p53, demonstrating that MAP17 may serve as a potential prognostic biomarker for PTC treatment.

Keywords: MAP17; NUMB; Papillary thyroid cancer; Tumorigenesis; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Protein Stability
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Neoplasms* / genetics
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • Membrane Proteins
  • PDZK1IP1 protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53