SNORA42 Promote Oesophageal Squamous Cell Carcinoma Development Through Interacting With Dhx9

Abstract

Background:Oesophageal squamous cell carcinoma (ESCC) is a high malignant cancer, which is the most common subtype of oesophageal cancer. Small nucleolar RNAs (snoRNAs) are a group of novel non-coding RNAs that have been found play a key role in various cancers. Methods:The expression of SNORA42 in ESCC samples and cell lines was measured by using real-time PCR and a series of in vitro and in vivo assays were performed to determine the function of SNORA42 in ESCC. Furthermore, RNA pull-down assay combined with Mass Spectrometry was applied to identify the protein that is associated with SNORA42. Silencing SNORA42 in ESCC cell followed by Next-Generation mRNA Sequencing was used to investigate the signaling pathway regulated by SNORA42.Results: We identified H/ACA box snoRNA42 (SNORA42) wasupregulated in ESCC and had the potential to be applied as a prognostic marker. Specifically, overexpression of SNORA42 promotedESCCprogressionin vitro and in vivo, whereas knockdown of SNORA42 had opposite effects. We identified SNORA42 interacted with DHX9, which was up-regulated in ESCC and had a positive correlation with the expression of SNORA42. Furthermore, the promotion of SNORA42 on ESCC phenotypes can be reversed by knockdown of DHX9. Mechanically, SNORA42 promoted DHX9 expression by attenuating DHX9 transports into cytoplasm, to protect DHX9 from being ubiquitinated and degraded. From 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 promotingthe transcriptional co-activator DHX9 interacted with p-p65, inducingNF-κB downstream genes expression. Conclusions:These findings suggest that SNORA42 is up-regulated in ESCC and promotes ESCC developments,partly via interacting with DHX9 and triggering SNORA42/DHX9/p65 axis.