HHIP overexpression inhibits the proliferation, migration and invasion of non-small cell lung cancer
HHIP overexpression inhibits the proliferation, migration and invasion of non-small cell lung cancer
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DOI：
10.1371/journal.pone.0225755
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发表时间：
2019-11-25
期刊：
影响因子：
3.7
通讯作者：
Ye, Wan-Li
中科院分区：
文献类型：
--
作者：
Zhao, Jian-Guo;Wang, Jian-Fang;Ye, Wan-Li
本研究的主要目的是探讨hedgehog相互作用蛋白（HHIP）过表达对非小细胞肺癌（NSCLC）细胞增殖、迁移和侵袭的影响。NSCLC组织和正常组织的HHIP基因表达数据来自Gene Expression Omnibus（GEO）的GSE 18842/GSE 19804/GSE 43458数据库。数据库，然后通过TCGA NSCLC数据库在1027例NSCLC患者和108例正常人的队列中进行验证。采用卡方检验分析HHIP表达与NSCLC临床病理特征的关系。实时定量PCR检测HHIP在NSCLC细胞中的表达水平。通过一系列体外试验研究HHIP的功能。结果在GEO数据库和TCGA数据库中，HHIP mRNA在NSCLC中表达均显著下调（P< 0.05）。通过qRT-PCR分析，在NSCLC细胞系中证实了这一结果，其在正常NSCLC细胞系BEAS-2B中的表达显著高于NSCLC细胞。卡方检验结果显示HHIP低表达与性别、肿瘤类型、TNM分期及肿瘤大小有关。功能实验结果显示，HHIP过表达可显著降低NSCLC细胞的增殖、迁移和侵袭能力（P< 0.05）。结论HHIP对NSCLC细胞的增殖、迁移和侵袭具有调节作用，可作为NSCLC分类和分期的判断标准。
ObjectiveThe primary purpose of this study is to investigate the effect of hedgehog-interacting protein (HHIP) overexpression on the proliferation, migration and invasion of non-small cell lung cancer (NSCLC).MethodsFirstly, HHIP gene expression data of NSCLC tissues and normal tissues were obtained from GSE18842/GSE19804/GSE43458 databases of the Gene Expression Omnibus (GEO) database and then validated by TCGA NSCLC database in a cohort of 1027 cases of NSCLC patients and 108 cases of normal people. A chi-square test was used to analyze the relationship between HHIP expression and clinicopathological characteristics of NSCLC. The expression levels of HHIP in NSCLC cells were detected by quantitative-real time PCR. The function of HHIP was investigated by a series of in vitro assays. CCK-8, wounding healing, Transwell invasion assay were utilized to explore the mechanisms of HHIP.ResultsHHIP mRNA were significantly down-regulated in NSCLC in three GEO databases and TCGA database (P< 0.05). This result was confirmed in NSCLC cell lines by qRT-PCR analysis, its expression in normal NSCLC cell line BEAS-2B was significantly higher than that in NSCLC cells. Chi-square test results showed that the low expression of HHIP was correlated with gender, cancer type, TNM stage and tumor size. Functional experimental results showed that over-expressing HHIP significantly decreased the ability of cell proliferation, migration and invasion in NSCLC cells (P< 0.05).ConclusionOverall, the above results indicated that HHIP could regulate proliferation, migration and invasion, and could be used as a judging criterion for identifying NSCLC classification and stage.