SNHG8 is identified as a key regulator in non-small-cell lung cancer progression sponging to miR-542-3p by targeting CCND1/CDK6.
SNHG8 is identified as a key regulator in non-small-cell lung cancer progression sponging to miR-542-3p by targeting CCND1/CDK6.
复制标题
SNHG8 被确定为非小细胞肺癌进展的关键调节因子，通过靶向 CCND1/CDK6 海绵化 miR-542-3p
DOI：
10.2147/ott.s170482
复制
发表时间：
2018
影响因子：
4
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Chen C;Zhang Z;Li J;Sun Y
最近，已知各种动态表达的lncRNA在癌症进展中起关键作用。核仁小RNA宿主基因（SNHG）是一种稳定的胞浆型lncRNA，在非小细胞肺癌（NSCLC）中起着癌基因的作用。SNHG 8作为SNHG的重要成员，在多种肿瘤中过表达，但在NSCLC中的生物学功能尚不清楚。本研究旨在探讨SNHG 8在NSCLC中的生物学功能及其作用机制。方法收集2014年1月至2014年12月期间收治的120例NSCLC患者，观察SNHG 8表达与NSCLC临床病理特征的关系。通过qRT-PCR分析SNHG 8在癌组织和细胞中的表达。CCK-8法检测细胞增殖能力。流式细胞仪检测细胞凋亡和细胞周期。采用荧光素酶法和Western blot法检测SNHG 8在NSCLC细胞中的作用机制。并通过裸鼠移植瘤实验检测SNHG 8的体内功能。SNHG 8在NSCLC组织和细胞中过表达。SNHG 8高表达患者的总生存期（OS）和无进展生存期（PFS）比SNHG 8低表达患者差。SNHG 8基因敲低可抑制NSCLC细胞的体外和体内增殖，通过靶向miR-542- 3 p/CCND 1/CDK 6将细胞周期阻滞在G 0/G1期，并通过激活Caspase-3诱导细胞凋亡。SNHG 8通过调节下游效应物（包括CCND 1和CDK 6）在NSCLC进展中负调控miR-542- 3 p。SNHG 8在NSCLC的治疗中显示出巨大的应用潜力。
Recently, various dynamically expressed lncRNAs are known to play critical roles in cancer progression. Small nucleolar RNA host genes (SNHG), a stable cytoplasmic lncRNA, which have been widely reported to act as an oncogene in non-small cell lung cancer (NSCLC). As an important member of SNHG, SNHG8 have been suggested to over-expressed in several cancer disease, while the biological function in NSCLC remains unclear. Here we investigated the biological function and underlying mechanism of SNHG8 in human NSCLC. The relationship between SNHG8 expression and clinicopathologic characteristic in NSCLC patients were observed from January 2014 to December 2014 in 120 NSCLC patients. The expression of SNHG8 were analyzed by qRT-PCR assay in cancer tissues and cells. Cell proliferation ability were detected in NSCLC cells by CCK-8 assay. Flow cytometric analysis were performed to detected the cell apoptosis and cell cycle. Luciferase assay and Western blot assay were performed on NSCLC cells to detected the underlying mechanism of SNHG8 in NSCLC. Moreover, Tumor xenografts in nude mice were performed to detected the in vivo function of SNHG8. SNHG8 was over-expressed in NSCLC tissues and cells. Patients with high SNHG8 expression have poorer overall survival (OS) and progression-free survival (PFS) than the patients with low SNHG8 expression. SNHG8 knockdown inhibited NSCLC cell proliferation in vitro and in vivo, arrested cell cycle in the G0/G1 phase via targeting miR-542-3p/CCND1/ CDK6, and induced cell apoptosis via activation of Caspase-3. SNHG8 negatively regulated miR-542-3p in NSCLC progression by regulating downstream effectors including CCND1 and CDK6. SNHG8 showed great potential for the application in the treatment of NSCLC.