SNORA42 promotes oesophageal squamous cell carcinoma development through triggering the DHX9/p65 axis

Genomics. 2021 Sep;113(5):3015-3029. doi: 10.1016/j.ygeno.2021.06.036. Epub 2021 Jun 26.


Small nucleolar RNAs (snoRNAs) are an important group of non-coding RNAs that have been reported to play a key role in the occurrence and development of various cancers. Here we demonstrate that Small nucleolar RNA 42 (SNORA42) enhanced the proliferation and migration of Oesophageal squamous carcinoma cells (ESCC) via the DHX9/p65 axis. Our results found that SNORA42 was significantly upregulated in ESCC cell lines, tissues and serum of ESCC patients. The high expression level of SNORA42 was positively correlated with malignant characteristics and over survival probability of patients with ESCC. Through in vitro and in vivo approaches, we demonstrated that knockdown of SNORA42 significantly impeded ESCC growth and metastasis whereas overexpression of SNORA42 got opposite effects. Mechanically, SNORA42 promoted DHX9 expression by attenuating DHX9 transports into the cytoplasm, to protect DHX9 from being ubiquitinated and degraded. From the KEGG analysis of Next-Generation Sequencing, the NF-κB pathway was one of the most regulated pathways by SNORA42. SNORA42 enhanced phosphorylation of p65 and this effect could be reversed by NF-κB inhibitor, BAY11-7082. Moreover, SNORA42 activated NF-κB signaling through promoting the transcriptional co-activator DHX9 interacted with p-p65, inducing NF-κB downstream gene expression. In summary, our study highlights the potential of SNORA42 is up-regulated in ESCC and promotes ESCC development partly via interacting with DHX9 and triggering the DHX9/p65 axis.

Keywords: DHX9; ESCC; SNORA42; Ubiquitination.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • DEAD-box RNA Helicases / pharmacology
  • Esophageal Neoplasms* / pathology
  • Esophageal Squamous Cell Carcinoma* / genetics
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • NF-kappa B / genetics
  • Neoplasm Proteins / metabolism
  • RNA, Small Nucleolar
  • Signal Transduction
  • Transcription Factor RelA


  • H-ACA box small nucleolar RNA 7A, human
  • NF-kappa B
  • Neoplasm Proteins
  • RELA protein, human
  • RNA, Small Nucleolar
  • Transcription Factor RelA
  • DHX9 protein, human
  • DEAD-box RNA Helicases