SNHG17/miR-384/ELF1 axis promotes cell growth by transcriptional regulation of CTNNB1 to activate Wnt/β-catenin pathway in oral squamous cell carcinoma
SNHG17/miR-384/ELF1 axis promotes cell growth by transcriptional regulation of CTNNB1 to activate Wnt/β-catenin pathway in oral squamous cell carcinoma
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DOI：
10.1038/s41417-021-00294-9
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发表时间：
2021-02-02
影响因子：
6.4
通讯作者：
Zheng, Mengdan
中科院分区：
文献类型：
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作者：
Qiao, Chunyan;Qiao, Tianyi;Zheng, Mengdan
越来越多的证据表明，长非编码RNA(Long Non-Coding RNAs，LncRNAs)在包括口腔鳞状细胞癌(OSCC)在内的多种人类恶性肿瘤中异常表达。然而，关于lncRNA小核仁RNA宿主基因17(SNHG17)在口腔鳞状细胞癌中的作用的探索有限。因此，SNHG17在口腔鳞癌细胞系中显著上调，并促进口腔鳞癌细胞的生长。进一步的机制研究，包括DNA/RNA下拉、RIP、CHIP和荧光素酶报告基因检测。已证实Wnt/β-catenin信号通路参与SNHG17介导的口腔鳞状细胞癌细胞生长。此外，E74类似Ets转录因子1(Elf1)是口腔鳞癌中CTNNB1(β-catenin mRNA)的转录激活子。受竞争内源RNAs(CeRNAs)网络的启发，我们惊喜地发现SNHG17和Elf1通过与microRNA-384(miR-384)竞争结合而在口腔鳞癌中作为ceRNAs发挥作用。通过挽救实验，我们发现SNHG17通过调节miR-384/Elf1轴促进OSCC细胞的生长。重要的是，我们证明了Elf1对于SNHG17影响的口腔鳞癌的进展是不可或缺的。综上所述，SNHG17/miR-384/Elf1轴通过促进CTNNB1的表达，从而激活Wnt/β-catenin信号通路，促进口腔鳞癌细胞的生长。
Increasing evidence proved the abnormal expression of long non-coding RNAs (lncRNAs) in various human malignancies, including oral squamous cell carcinoma (OSCC). Nevertheless, limited explorations concern the role of lncRNA small nucleolar RNA host gene 17 (SNHG17) in OSCC. Herein, SNHG17 was disclosed to be remarkably upregulated in OSCC cell lines and promoted OSCC cell growth. Further mechanistic studies, including DNA/RNA pull down, RIP, ChIP, and luciferase reporter gene assays, were conducted. It was confirmed that Wnt/beta-catenin signaling pathway was involved in the SNHG17-mediated OSCC cell growth. Moreover, E74 like ETS transcription factor 1 (ELF1) was identified as the transcription activator of CTNNB1 (beta-catenin mRNA) in OSCC. Inspired by competing for endogenous RNAs (ceRNAs) network, we were pleasantly surprised to find that SNHG17 and ELF1 functioned as ceRNAs in OSCC via competitively binding to microRNA-384 (miR-384). By using rescue assays, we revealed that SNHG17 facilitated OSCC cell growth through modulating miR-384/ELF1 axis. Importantly, we certified that ELF1 was indispensable for SNHG17-affected OSCC progression. Collectively, it can be concluded that SNHG17/miR-384/ELF1 axis contributed to OSCC cell growth via promoting CTNNB1 expression, thus activating Wnt/beta-catenin signaling pathway.