Shan Yanan, Wei Sisi, Xiang Xiaohan, Dai Suli, Cui Wenxuan, Zhao Riyang, Zhang Cong, Zhang Weimin, Zhao Lianmei, Shan Baoen
Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China.
State Key Laboratory of Molecular Oncology, Cancer institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
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.
小核仁RNA（snoRNAs）是一类重要的非编码RNA，据报道在各种癌症的发生和发展中起关键作用。在此我们证明，小核仁RNA 42（SNORA42）通过DHX9/p65轴增强食管鳞状癌细胞（ESCC）的增殖和迁移。我们的研究结果发现，SNORA42在ESCC细胞系、组织及ESCC患者血清中显著上调。SNORA42的高表达水平与ESCC患者的恶性特征及较高的生存概率呈正相关。通过体内外实验方法，我们证明敲低SNORA42可显著抑制ESCC的生长和转移，而SNORA42的过表达则产生相反的效果。机制上，SNORA42通过减少DHX9向细胞质的转运来促进DHX9的表达，从而保护DHX9不被泛素化和降解。从下一代测序的KEGG分析来看，NF-κB通路是受SNORA42调控最显著的通路之一。SNORA42增强p65的磷酸化，这种作用可被NF-κB抑制剂BAY11-7082逆转。此外，SNORA42通过促进转录共激活因子DHX9与p-p65相互作用来激活NF-κB信号，诱导NF-κB下游基因表达。总之，我们的研究强调了SNORA42在ESCC中上调的潜在作用，并且部分通过与DHX9相互作用并触发DHX9/p65轴来促进ESCC的发展。
