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长链非编码 RNA SNHG16 预测 ESCC 预后不良,并通过调节 Wnt/β-连环蛋白信号通路促进细胞增殖和侵袭。

LncRNA SNHG16 predicts poor prognosis in ESCC and promotes cell proliferation and invasion by regulating Wnt/β-catenin signaling pathway.

机构信息

Department of Oncology, Taizhou People's Hospital, Taizhou, Jiangsu, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Jun;22(12):3795-3803. doi: 10.26355/eurrev_201806_15262.

Abstract

OBJECTIVE

Increasing evidence indicated that small nucleolar RNA host gene 16 (SNHG16) acted as a key regulator in the proliferation and metastasis of several cancers, including esophageal squamous cell carcinoma (ESCC). In this research, we aimed to explore biological functions, clinical significance and the underlying molecular mechanisms of SNHG16 in ESCC.

PATIENTS AND METHODS

qRT-PCR was performed to examine the expression of SNHG16 in ESCC cell lines and clinical ESCC tissue samples. The association of SNHG16 expression with clinicopathological factors and prognosis was statistically analyzed. Cell Counting Kit-8, flow cytometry, and transwell invasion assays were performed to determine the effect of SNHG16 in the regulation of biological behaviors of ESCC cells. Luciferase assay and Western blot were performed to determine the activation of Wnt/β-catenin signaling pathway RESULTS: We observed that SNHG16 expression levels were significantly upregulated in ESCC tissues and cell lines compared with the corresponding normal tissues and normal esophageal cell line, respectively. In addition, increased expression of SNHG16 were strongly linked to tumor stage (p = 0.019), lymph nodes metastasis (p = 0.007) and clinical stage (p = 0.026). Kaplan-Meier assay showed that the survival time of patients with high SNHG16 expression was significantly shorter than those with low SNHG16 expression (p = 0.0017). Univariate and multivariate analyses showed that high SNHG16 expression in ESCC was an independent predictor of poor survival. Loss-of-function experiments revealed that knockdown of SNHG16 suppressed proliferation and invasion and induced apoptosis of ESCC cells. Mechanistically, Wnt/β-catenin signaling pathways were actively modulated by SNHG16 in ESCC cells.

CONCLUSIONS

Our findings reveal that SNHG16 plays an important role in ESCC proliferation/metastasis via modulating Wnt/β-catenin signaling pathways and could represent a novel biomarker for predicting poor survival as well a promising therapeutic target.

摘要

目的

越来越多的证据表明,小核仁 RNA 宿主基因 16(SNHG16)在几种癌症(包括食管鳞状细胞癌[ESCC])的增殖和转移中充当关键调节因子。在这项研究中,我们旨在探讨 SNHG16 在 ESCC 中的生物学功能、临床意义和潜在的分子机制。

患者和方法

使用 qRT-PCR 检测 ESCC 细胞系和临床 ESCC 组织样本中 SNHG16 的表达。统计分析 SNHG16 表达与临床病理因素和预后的关系。使用细胞计数试剂盒-8、流式细胞术和 Transwell 侵袭实验来确定 SNHG16 对 ESCC 细胞生物学行为的调节作用。进行荧光素酶测定和 Western blot 以确定 Wnt/β-catenin 信号通路的激活情况。

结果

我们观察到,与相应的正常组织和正常食管细胞系相比,SNHG16 的表达水平在 ESCC 组织和细胞系中明显上调。此外,SNHG16 的表达增加与肿瘤分期(p = 0.019)、淋巴结转移(p = 0.007)和临床分期(p = 0.026)密切相关。Kaplan-Meier 分析表明,SNHG16 高表达的患者的生存时间明显短于 SNHG16 低表达的患者(p = 0.0017)。单因素和多因素分析表明,ESCC 中 SNHG16 的高表达是预后不良的独立预测因素。功能丧失实验表明,SNHG16 的敲低抑制 ESCC 细胞的增殖和侵袭并诱导细胞凋亡。机制上,SNHG16 可在 ESCC 细胞中主动调节 Wnt/β-catenin 信号通路。

结论

我们的研究结果表明,SNHG16 通过调节 Wnt/β-catenin 信号通路在 ESCC 的增殖/转移中发挥重要作用,可作为预测不良预后的新生物标志物,也是有前途的治疗靶点。

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