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Up-regulation of lncRNA SNHG1 indicates poor prognosis and promotes cell proliferation and metastasis of colorectal cancer by activation of the Wnt/β-catenin signaling pathway

机译:lncRNA SNHG1的上调指示预后不良并通过激活Wnt /β-catenin信号通路促进结直肠癌的细胞增殖和转移

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摘要

Recently, the lncRNA small nucleolar RNA host gene (SNHG1) has been exhibited to be upregulated, which plays a crucial role in the development and prognosis of several cancers. However, the role of the biology and clinical significance of SNHG1 in the tumorigenesis of colorectal cancer (CRC) has rarely been reported. In this work, we firstly found that SNHG1 expression levels were upregulated aberrantly in colorectal cancer tissues and colorectal cancer cell lines. By Kaplan-Meier survival analysis, patients with high SNHG1 expression level had poorer overall survival (OS) and progression-free survival (PFS) than those with low SNHG1 expression. In multivariate analysis, increased SNHG1 expression was proved to be an independent unfavorable prognostic indicator for CRC. In vitro experiments revealed that SNHG1 silencing inhibited the growth and metastasis and induced apoptosis of CRC cell lines. Finally, we found that SNHG1 may induce the activation of the WNT/β-catenin pathway through regulating β-catenin expression and transcription factor-4 (TCF-4), cyclin D1 and MMP-9. Altogether, our findings demonstrated that lncRNA SNHG1, was high expressed in colorectal cancer tissues and may serve as a tumor oncogene through regulating WNT/β-catenin signal pathway, which provided a candidate diagnostic biomarker and a promising therapeutic target for patients with CRC.
机译:最近,lncRNA小核仁RNA宿主基因(SNHG1)已被证明是上调的,它在几种癌症的发生和预后中起着至关重要的作用。然而,很少有人报道SNHG1在大肠癌(CRC)的肿瘤发生中的生物学作用和临床意义。在这项工作中,我们首先发现在结直肠癌组织和结直肠癌细胞系中SNHG1表达水平异常上调。通过Kaplan-Meier生存分析,与SNHG1表达低的患者相比,SNHG1表达高的患者的总生存期(OS)和无进展生存期(PFS)差。在多变量分析中,增加的SNHG1表达被证明是CRC的独立不利预后指标。体外实验显示,SNHG1沉默可抑制CRC细胞系的生长和转移并诱导其凋亡。最后,我们发现SNHG1可能通过调节β-catenin表达和转录因子4(TCF-4),cyclin D1和MMP-9来诱导WNT /β-catenin途径的激活。总之,我们的发现表明,lncRNA SNHG1在大肠癌组织中高表达,并可能通过调节WNT /β-catenin信号通路而成为肿瘤癌基因,为CRC患者提供了候选的诊断生物标志物和有希望的治疗靶标。

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