Long noncoding RNA LINC01133 inhibits oral squamous cell carcinoma metastasis through a feedback regulation loop with GDF15
Long noncoding RNA LINC01133 inhibits oral squamous cell carcinoma metastasis through a feedback regulation loop with GDF15
复制标题
DOI：
10.1002/jso.25278
复制
发表时间：
2018-12-01
影响因子：
2.5
通讯作者：
Wang, Huiming
中科院分区：
文献类型：
--
作者：
Kong, Jianlu;Sun, Wenjie;Wang, Huiming
背景与目的方法长链非编码rna （lncRNAs）在肿瘤转移过程中起关键作用。我们的目的是研究lncRNA LINC01133在口腔鳞状细胞癌（OSCC）转移中的作用。采用实时定量聚合酶链式反应（RT-qPCR）检测OSCC患者组织样本和OSCC细胞系中LINC01133和生长与分化因子15 （GDF15）的RNA水平。应用SPSS20.0统计分析临床样本中LINC01133的表达及LINC01133与GDF15的相关性表达。通过transwell试验评估细胞迁移/侵袭。采用RNA-seq筛选LINC01133下游基因，RT-qPCR验证。Western blot检测GDF15蛋白水平。结果结论LINC01133在OSCCs中表达下调；LINC01133在OSCCs中的高表达与较少的转移和较好的预后相关。LINC01133抑制OSCC细胞的迁移和侵袭。RNA-seq数据显示，LINC01133对GDF15有抑制作用，GDF15可以恢复LINC01133对OSCC细胞迁移和侵袭的抑制作用。有趣的是，GDF15也抑制LINC01133。此外，临床研究证实了LINC01133与GDF15的表达呈显著负相关。综上所述，这些数据表明LINC01133通过与GDF15相互抑制的反馈调节回路抑制OSCC转移，提示了一种新的OSCC诊断和治疗靶点。
Background and Objectives Methods Long noncoding RNAs (lncRNAs) play key roles in carcinoma metastasis. We aimed to investigate lncRNA LINC01133 in oral squamous cell carcinoma (OSCC) metastasis. The RNA levels of LINC01133 and growth and differentiation factor 15 (GDF15) in tissue samples from OSCC patients, and OSCC cell lines were tested by real-time quantitative polymerase chain reaction (RT-qPCR). SPSS20.0 was used to perform statistical analysis of LINC01133 expression in clinical samples and correlate expression of LINC01133 and GDF15. Cell migration/invasion was assessed via transwell assays. Downstream genes of LINC01133 were screened using RNA-seq and validated by RT-qPCR. GDF15 protein levels were evaluated via Western blot analysis. Results Conclusions LINC01133 was downregulated in OSCCs; higher expression of LINC01133 in OSCCs was correlated with less metastasis and better prognosis. LINC01133 inhibited OSCC cell migration and invasion. RNA-seq data showed that LINC01133 inhibited GDF15, and GDF15 could rescue inhibition of OSCC cell migration and invasion caused by LINC01133. Interestingly, GDF15 also inhibited LINC01133. Furthermore, a significant negative correlation between expression of LINC01133 and GDF15 was validated in the clinical study. Collectively, these data indicate that LINC01133 inhibited OSCC metastasis via a feedback regulation loop of reciprocal inhibition with GDF15, suggesting a new diagnostic and therapeutic target for OSCC.