Ma Tianshi, Ma Hongwei, Zou Zigui, He Xuezhi, Liu Yanhua, Shuai You, Xie Min, Zhang Zhihong
Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Pathology, Zhenjiang First people's hospital, Zhenjiang, China.
Cell Physiol Biochem. 2018;45(4):1566-1580. doi: 10.1159/000487693. Epub 2018 Feb 21.
BACKGROUND/AIMS: Lung cancer (LC) is a serious disease with high morbidity and mortality. Long noncoding RNAs (lncRNAs) have garnered attention because they participate in diverse human disorders, including cancer. Our study examined the long intergenic noncoding RNA 00707 (LINC00707). The effects of LINC00707 on lung adenocarcinoma (LAD) and molecular mechanisms are unclear. This study is aimed to investigate the role of LINC00707 in the malignant processes of LAD.
Quantitative reverse transcription PCR (qRT-PCR) was used to examine the expression level of LINC00707 in tissues and cell lines. The association of LINC00707 expression and postoperative prognosis was analyzed by the Kaplan-Meier method and log-rank test. Cell proliferation was evaluated in vitro and in vivo. Transwell assays were performed to examine cell migration. Cell cycle and apoptosis was determined by flow -cytometric and western blot analyses. Microarray analysis was conducted to screen for the downstream target gene Cdc42 of LINC00707, which was identified by qRT-PCR, functional analysis, and rescue experiment.
The expression level of LINC00707 was clearly upregulated in LAD tissues compared to that in corresponding normal tissues. Its overexpression was related to advanced TNM stage, larger tumor size, lymphatic metastasis, and poor prognosis. Functional assays revealed that LINC00707 knockdown repressed LAD cell proliferation both in vitro and in vivo. This process may involve the inducing of G1 arrest and apoptosis. Moreover, cell migration was impaired after LINC00707 inhibition. Microarray analysis and rescue assays suggested that Cdc42 is an important target gene involved in the carcinogenesis of LINC00707.
In summary, LINC00707 is a noncoding oncogene that exerts important regulatory functions in LAD, suggesting its potential as a biomarker in the prognosis and treatment of LAD.
背景/目的：肺癌（LC）是一种发病率和死亡率都很高的严重疾病。长链非编码RNA（lncRNAs）因其参与包括癌症在内的多种人类疾病而受到关注。我们的研究检测了长链基因间非编码RNA 00707（LINC00707）。LINC00707对肺腺癌（LAD）的影响及其分子机制尚不清楚。本研究旨在探讨LINC00707在LAD恶性进程中的作用。
采用定量逆转录PCR（qRT-PCR）检测组织和细胞系中LINC00707的表达水平。采用Kaplan-Meier法和对数秩检验分析LINC00707表达与术后预后的关系。在体外和体内评估细胞增殖。进行Transwell实验检测细胞迁移。通过流式细胞术和蛋白质印迹分析确定细胞周期和细胞凋亡情况。进行基因芯片分析以筛选LINC00707的下游靶基因Cdc42，并通过qRT-PCR、功能分析和拯救实验对其进行鉴定。
与相应正常组织相比，LINC00707在LAD组织中的表达水平明显上调。其过表达与晚期TNM分期、更大的肿瘤大小、淋巴转移及预后不良有关。功能分析显示，敲低LINC00707在体外和体内均能抑制LAD细胞增殖。这一过程可能涉及诱导G1期阻滞和细胞凋亡。此外，抑制LINC00707后细胞迁移受到损害。基因芯片分析和拯救实验表明，Cdc42是参与LINC00707致癌过程的重要靶基因。
总之，LINC00707是一种非编码癌基因，在LAD中发挥重要的调控功能，提示其在LAD预后和治疗中作为生物标志物的潜力。
