长链非编码 RNA SNHG1 通过 Notch1 信号通路促进喉癌细胞增殖。
LncRNA SNHG1 promotes cell proliferation in laryngeal cancer via Notch1 signaling pathway.
机构信息
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Aug;23(15):6562-6569. doi: 10.26355/eurrev_201908_18542.
OBJECTIVE
We aimed at elucidating the potential function of long noncoding ribonucleic acids (lncRNAs) small nucleolar RNA host gene 1 (SNHG1) in the progression of laryngeal cancer (LC) and its underlying mechanism.
PATIENTS AND METHODS
Relative level of SNHG1 in LC tissues and controls was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Its expression in LC patients with different tumor stages and statues of lymph node metastasis was examined as well. Correlation between SNHG1 expression and prognosis of LC patients was evaluated by the Kaplan-Meier method. SNHG1 siRNA (si-SNHG1) was constructed for downregulation of SNHG1 expression. Potential effects of downregulated SNHG1 on viability and proliferation of LC cells were detected by cell counting kit-8 (CCK-8) and colony formation assay, respectively. After knockdown of SNHG1, relative levels of Notch1 and hairy, and enhancer of split homolog-1 (Hes1) were determined by qRT-PCR and Western blot. Regulatory effects of SNHG1/Notch1 axis on biological behaviors of LC were finally evaluated.
RESULTS
SNHG1 was upregulated in LC tissues than that of controls. Besides, its level was higher in LC with T3-T4 relative to those of T1-T2. Higher abundance of SNHG1 was identified in LC patients with lymph node metastasis compared with those non-metastatic patients. Survival analysis indicated that LC patients with high-level SNHG1 had worse overall survival. Knockdown of SNHG1 in Tu212 and Hep2 cells downregulated relative levels of Notch1 and Hes1. Moreover, SNHG1 knockdown resulted in decreased viability and proliferative ability of LC cells. Notch1 overexpression could reverse the regulatory effects of SNHG1 on viability and proliferation of LC cells.
CONCLUSIONS
LncRNA SNHG1 is highly expressed in LC tissues. It promotes the proliferation of LC cells by inhibiting Notch1 pathway, thereby promoting the progression of LC.
目的
本研究旨在阐明长链非编码 RNA（lncRNA）小核仁 RNA 宿主基因 1（SNHG1）在喉癌（LC）进展中的潜在功能及其作用机制。
方法
采用实时定量聚合酶链反应（qRT-PCR）检测 LC 组织和对照组织中 SNHG1 的相对水平。检测不同肿瘤分期和淋巴结转移状态的 LC 患者中 SNHG1 的表达情况。通过 Kaplan-Meier 方法评估 SNHG1 表达与 LC 患者预后的相关性。构建 SNHG1 siRNA（si-SNHG1）下调 SNHG1 表达。通过细胞计数试剂盒-8（CCK-8）和集落形成实验分别检测下调 SNHG1 对 LC 细胞活力和增殖的潜在影响。敲低 SNHG1 后，通过 qRT-PCR 和 Western blot 检测 Notch1 和 hairy、增强子分裂同源物-1（Hes1）的相对水平。最后，评估 SNHG1/Notch1 轴对 LC 生物学行为的调节作用。
结果
与对照相比，SNHG1 在 LC 组织中上调。此外，与 T1-T2 相比，T3-T4 的 LC 中 SNHG1 的水平更高。与无淋巴结转移的患者相比，有淋巴结转移的 LC 患者 SNHG1 丰度更高。生存分析表明，高水平 SNHG1 的 LC 患者总生存期较差。Tu212 和 Hep2 细胞中 SNHG1 的敲低下调了 Notch1 和 Hes1 的相对水平。此外，SNHG1 敲低导致 LC 细胞活力和增殖能力下降。Notch1 过表达可逆转 SNHG1 对 LC 细胞活力和增殖的调节作用。
结论
lncRNA SNHG1 在 LC 组织中高表达。它通过抑制 Notch1 通路促进 LC 细胞的增殖，从而促进 LC 的进展。
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