长链非编码 RNA SNHG1 通过上调 EZH2 和抑制 KLF2 转录促进膀胱癌进展。
Long non-coding RNA SNHG1 promotes bladder cancer progression by upregulating EZH2 and repressing KLF2 transcription.
机构信息
Department of Urology, The Second Hospital of Anhui Medical University, Hefei, Anhui, China.
Department of Urology, The Second Hospital of Anhui Medical University, Hefei, Anhui, China.
出版信息
Clinics (Sao Paulo). 2022 Sep 7;77:100081. doi: 10.1016/j.clinsp.2022.100081. eCollection 2022.
OBJECTIVE
Long Non-Coding RNAs (LncRNAs) act as an indispensable role in cancer development. The study aimed to investigate the role and mechanism of lncRNA Small Nucleolar RNA Host Gene 1 (SNHG1) in Bladder Cancer (BC) progression.
METHOD
The expression, prognostic value, diagnostic value, and correlation of SNHG1, Enhancer of Zeste 2 polycomb repressive complex 2 subunit (EZH2), and Kruppel Like Factor 2 (KLF2) were analyzed through bioinformatics analysis. The expression was also validated in BC tissues and cell lines. Besides, their regulation and binding were tested via qPCR, Western blot, Dual-Luciferase Reporter Assay (DLRA), Argonaute RISC catalytic component 2-RNA Immunoprecipitation (AGO2-RIP), and Chromatin Immunoprecipitation (ChIP). A xenograft model in nude mice was also established.
RESULTS
SNHG1 was significantly overexpressed in BC tissues and cells. Importantly, SNHG1 was associated with poor survival, and ROC curves revealed high diagnostic values. Moreover, by CCK8, wound healing, transwell, and Western blot analysis, SNHG1 knockdown significantly inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of BC cells. Additionally, in vivo experiments showed that silencing SNHG1 hindered tumorigenesis and tumor growth. Regarding mechanism, the results of AGO2-RIP, ChIP or DLRA showed that SNHG1 played different roles at diverse subcellular sites. In the cytoplasm, SNHG1 acted as a competing endogenous RNA for miR-137-3p to promote EZH2 expression. In the nucleus, SNHG1 could interact with EZH2 to inhibit KLF2 transcription.
CONCLUSION
Our study elucidated that SNHG1 formed a regulatory network and played an oncogenic role in BC, which provided a novel therapeutic target for BC treatment.
目的
长链非编码 RNA（lncRNAs）在癌症发展中发挥着不可或缺的作用。本研究旨在探讨 lncRNA 小核仁 RNA 宿主基因 1（SNHG1）在膀胱癌（BC）进展中的作用和机制。
方法
通过生物信息学分析，分析 SNHG1、增强子的表达、预后价值、诊断价值和相关性Zeste 2 多梳抑制复合物 2 亚基（EZH2）和 Kruppel 样因子 2（KLF2）。还验证了 BC 组织和细胞系中的表达。此外，通过 qPCR、Western blot、双荧光素酶报告基因分析（DLRA）、Argonaute RISC 催化成分 2-RNA 免疫沉淀（AGO2-RIP）和染色质免疫沉淀（ChIP）测试了它们的调节和结合。还建立了裸鼠异种移植模型。
结果
SNHG1 在 BC 组织和细胞中表达显著上调。重要的是，SNHG1与不良预后相关，ROC 曲线显示出较高的诊断价值。此外，通过 CCK8、划痕愈合、Transwell 和 Western blot 分析，SNHG1 敲低显著抑制了 BC 细胞的增殖、迁移、侵袭和上皮-间充质转化。此外，体内实验表明，沉默 SNHG1 抑制了肿瘤发生和肿瘤生长。关于机制，AGO2-RIP、ChIP 或 DLRA 的结果表明，SNHG1 在不同的亚细胞部位发挥不同的作用。在细胞质中，SNHG1 作为 miR-137-3p 的竞争性内源 RNA 促进 EZH2 表达。在核内，SNHG1 可以与 EZH2 相互作用抑制 KLF2 转录。
结论
本研究阐明了 SNHG1 在 BC 中形成了一个调控网络并发挥致癌作用，为 BC 治疗提供了一个新的治疗靶点。
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