SNHG1 的下调通过调节 Notch 信号通路抑制食管鳞状细胞癌中的细胞增殖和侵袭。
Downregulation of SNHG1 suppresses cell proliferation and invasion by regulating Notch signaling pathway in esophageal squamous cell cancer.
机构信息
Department of Thoracic, Jilin Cancer Hospital, Changchun, Jilin, China.
Department of Pharmacy, Jilin Cancer Hospital, Changchun, Jilin, China.
出版信息
Cancer Biomark. 2017 Dec 12;21(1):89-96. doi: 10.3233/CBM-170286.
BACKGROUND
Long non-coding RNAs (lncRNAs) exert important functions involved in tumorigenesis and cancer progression including esophageal squamous cell cancer (ESCC), however, the clinical role and underlying biological function of Small Nucleolar RNA Host Gene 1 (SNHG1) in ESCC is not well known.
METHODS
Quantitative Real-time polymerase chain reaction (QRT-PCR) was used to detect the SNHG1 expression levels in ESCC tissues and adjacent non-cancerous tissues. Chi-square test was used to evaluate the association between clinicopathological features and SNHG1 expression in ESCC patients, Kaplan-Meier curve and log rank test was performed to analyze the association between overall survival and SNHG1 expression. Cell proliferation and invasion was assessed by MTT assay, colony formation, and transwell cell invasion assays. Western blot were also performed to examine protein expression levels of E-cadherin, Vimentin and N-cadherin, Notch 1 and Hes-1.
RESULTS
We demonstrated that lncRNA SNHG1 was significantly up-regulated in ESCC tissues compared with adjacent non-cancerous tissues in ESCC patients. Meanwhile, increased lncRNA SNHG1 expression levels markedly correlated with lymph node metastasis, depth of invasion, TNM stage and reduced over survival time in ESCC patients. Furthermore, MTT assay, colony formation, transwell cell invasion, qRT-PCR and Western-blot assays demonstrated that knockdown of lncRNA SNHG1 could inhibit cell proliferation and cell invasion capacity and cell Epithelial-Mesenchymal Transition (EMT) phenomenon by up-regulation E-cadherin and down-regulating Vimentin and N-cadherin in ESCC cells. Besides, we demonstrated that knockdown of SNHG1 suppressed the Notch signaling pathway by reducing the Notch1 and Hes-1 expression levels in ESCC cells.
CONCLUSIONS
These results indicated that lncRNA SNHG1 may be a potential predictor of prognosis in ESCC patients and a novel target for ESCC treatment.
背景
长链非编码 RNA（lncRNAs）在肿瘤发生和癌症进展中发挥重要作用，包括食管鳞状细胞癌（ESCC），然而，小核仁 RNA 宿主基因 1（SNHG1）在 ESCC 中的临床作用和潜在生物学功能尚不清楚。
方法
采用实时定量聚合酶链反应（QRT-PCR）检测 ESCC 组织和相邻非癌组织中 SNHG1 的表达水平。采用卡方检验评估 ESCC 患者临床病理特征与 SNHG1 表达的关系，采用 Kaplan-Meier 曲线和对数秩检验分析总生存期与 SNHG1 表达的关系。采用 MTT 法、集落形成实验和 Transwell 细胞侵袭实验评估细胞增殖和侵袭能力。还进行了 Western blot 检测 E-cadherin、Vimentin 和 N-cadherin、Notch1 和 Hes-1 的蛋白表达水平。
结果
我们发现，与 ESCC 患者的相邻非癌组织相比，ESCC 组织中 lncRNA SNHG1 显著上调。同时，lncRNA SNHG1 表达水平的升高与淋巴结转移、浸润深度、TNM 分期和 ESCC 患者的生存时间缩短显著相关。此外，MTT 法、集落形成实验、Transwell 细胞侵袭实验、qRT-PCR 和 Western blot 实验表明，在 ESCC 细胞中敲低 lncRNA SNHG1 可通过上调 E-cadherin 下调 Vimentin 和 N-cadherin 抑制细胞增殖和细胞侵袭能力和细胞上皮间质转化（EMT）现象。此外，我们还发现，在 ESCC 细胞中敲低 SNHG1 可通过降低 Notch1 和 Hes-1 的表达水平抑制 Notch 信号通路。
结论
这些结果表明，lncRNA SNHG1 可能是 ESCC 患者预后的潜在预测因子，也是 ESCC 治疗的新靶点。
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