背景:大量研究表明,长链非编码RNA(lncRNAs)与许多疾病和癌症的发生发展密切相关。然而,它们在食管鳞状细胞癌(ESCC)中的特定生物学功能和分子机制尚不清楚。
方法:进行RNA-Seq以确定ESCC中lncRNAs的差异表达,在ESCC和上皮内瘤变(IEN)样本中检测到SNHG16的表达水平。进行了体外和体内实验以探索SNHG16的作用以及EIF4A3和Ras同源家族成员U(RhoU)信号传导的相互作用。
结果:通过RNA-Seq鉴定出一百七十五个上调的lncRNAs和134个下调的lncRNAs。SNHG16在ESCC和上皮内瘤变(IEN)样品中高表达,其表达水平与肿瘤分化程度和T分期有关。SNHG16的过表达可以促进ESCC细胞的增殖和转移。机械上,我们注意到SNHG16可以结合RNA结合蛋白(RBP)-真核翻译起始因子(EIF4A3)并与其相互作用形成复合物。重要的是,SNHG16和EIF4A3的联盟最终调控了Ras同源家族成员U(RhoU)。SNHG16通过招募EIF4A3调节RhoUmRNA的稳定性来调节RhoU表达。敲除RhoU进一步减轻了SNHG16癌基因在ESCC细胞中的作用。
结论:新鉴定的SNHG16-EIF4A3-RhoU信号通路直接协调ESCC发病机制中的反应,并表明SNHG16是潜在ESCC治疗的有希望的靶标。
BACKGROUND: Numerous studies have revealed that long noncoding RNAs (lncRNAs) are closely related to the development of many diseases and carcinogenesis. However, their specific biological function and molecular mechanism in oesophageal squamous cell carcinoma (ESCC) remains unclear.
METHODS: RNA-Seq was performed to determine the differential expressions of lncRNAs in ESCC, and the level of SNHG16 expression was detected in ESCC and intraepithelial neoplasia (IEN) samples. In vitro and in vivo experiments were performed to explore the role of SNHG16 and the interaction of EIF4A3 and Ras homologue family member U (
RhoU) signalling.
RESULTS: One hundred and seventy-five upregulated and 134 downregulated lncRNAs were identified by RNA-Seq. SNHG16 was highly expressed in ESCC and intraepithelial neoplasia (IEN) samples, and its expression level was correlated with tumour differentiation and T stage. Overexpression of SNHG16 can facilitate ESCC cell proliferation and metastasis. Mechanistically, we noticed that SNHG16 could bind RNA binding protein (RBP)-eukaryotic translation initiation factor (EIF4A3) and interact with it to form a complex. Importantly, the coalition of SNHG16 and EIF4A3 ultimately regulated Ras homologue family member U (
RhoU). SNHG16 modulated
RhoU expression by recruiting EIF4A3 to regulate the stability of
RhoU mRNA. Knockdown of
RhoU further alleviated the effect of the SNHG16 oncogene in ESCC cells.
CONCLUSIONS: The newly identified SNHG16-EIF4A3-
RhoU signalling pathway directly coordinates the response in ESCC pathogenesis and suggests that SNHG16 is a promising target for potential ESCC treatment.