Mechanism of HOXA10 in nasopharyngeal carcinoma cell proliferation through the PTPRG-AS1/USP1 axis

J Biochem Mol Toxicol. 2024 Nov;38(11):e70025. doi: 10.1002/jbt.70025.

Abstract

Nasopharyngeal carcinoma (NPC) is an epithelial carcinoma arising from the nasopharyngeal mucosal lining. The present study sought to analyze the mechanism by which homeobox A10 (HOXA10) affects NPC cell proliferation. The expression levels of HOXA10/long noncoding RNA (lncRNA) PTPRG antisense RNA 1 (PTPRG-AS1)/ubiquitin-specific peptidase 1 (USP1) in NPC tissues and cells were determined. Cell proliferation was evaluated. The enrichment of HOXA10 on the PTPRG-AS1 promoter was determined. The binding of PTPRG-AS1, HuR, and USP1 to each other was analyzed via RNA immunoprecipitation. USP1 mRNA stability was determined after actinomycin D treatment. The role of the PTPRG-AS1/USP1 axis in NPC cell proliferation was analyzed in combined experiments. The role of HOXA10 in vivo was confirmed in xenograft tumor models. The results revealed that HOXA10 was overexpressed in NPC. HOXA10 downregulation reduced NPC cell proliferation. PTPRG-AS1 and USP1 were upregulated in NPC. HOXA10 bound to the PTPRG-AS1 promoter to increase PTPRG-AS1 expression, and the binding of PTPRG-AS1 to HuR increased USP1 expression. PTPRG-AS1 or USP1 overexpression attenuated the inhibitory effects of HOXA10 downregulation on NPC cell proliferation. HOXA10 downregulation inhibited in vivo NPC proliferation through the PTPRG-AS1/USP1 axis. In conclusion, HOXA10 facilitates NPC cell proliferation in vitro and in vivo through the PTPRG-AS1/USP1 axis.

Keywords: HOXA10; HuR; PTPRG‐AS1; USP1; nasopharyngeal carcinoma.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeobox A10 Proteins* / genetics
  • Homeobox A10 Proteins* / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nasopharyngeal Carcinoma* / genetics
  • Nasopharyngeal Carcinoma* / metabolism
  • Nasopharyngeal Carcinoma* / pathology
  • Nasopharyngeal Neoplasms* / genetics
  • Nasopharyngeal Neoplasms* / metabolism
  • Nasopharyngeal Neoplasms* / pathology
  • RNA, Antisense
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / metabolism
  • Ubiquitin-Specific Proteases / genetics
  • Ubiquitin-Specific Proteases / metabolism

Substances

  • Homeobox A10 Proteins
  • HOXA10 protein, human
  • PTPRG protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5
  • RNA, Long Noncoding
  • Ubiquitin-Specific Proteases
  • USP1 protein, human
  • RNA, Antisense