胸膜转移性肺癌环状RNA表达谱及其临床意义

Differentially expressed circular RNAs in human pleural metastatic lung cancer and clinical significance

目的探讨环状RNA(circRNA)在胸膜转移性肺癌和胸膜结核表达谱中的差异。方法利用circRNA芯片技术检测3例胸膜转移性肺癌和胸膜结核患者的表达谱,经过对原始数据进行预处理,均一化后,找出差异表达的circRNA,经qRT-PCR进行验证。根据表达差异倍数较高和样本间一致性较好的原则筛选circRNA,借助生物信息学软件预测可能受其调控的miRNA,结合文献检索初步确定可能在胸膜转移性肺癌中具有重要作用的circRNA。结果与胸膜结核比较,胸膜转移性肺癌中1.5倍以上变化,并且差异有统计学意义的circRNA定义为差异表达的circRNA。胸膜转移性肺癌中,1.5倍以上变化且P≤0.05的circRNA共3条,其中上调2条,下调1条。分别为在胸膜转移性肺癌中明显上调的hsa-circ-103212(1.671倍,P=0.0245)、hsa-circ-104822(1.514倍,P=0.0478)和明显下调的hsa-circ-100548(1.808倍,P=0.0287)。生物信息学分析和文献检索显示,hsa-miR-613和hsa-miR-24-3p可能受hsa-circRNA-104822的调控而影响肺癌的发生、发展和转移。结论与胸膜结核比较,胸膜转移性肺癌circRNA表达谱发生了显著变化;hsa-circRNA-104822可能在肺癌、发展和转移中起重要作用。

Objective To analyze the difference of circular RNA( circRNA) expression profiles between pleural metastatic lung cancer and pleural tuberculosis. Methods The circRNA expression profiles in3 paired specimens of pleural metastatic lung cancer and pleural tuberculosis were detected using the human circRNA microarray. After preprocessing and homogenization of the original data,the differentially expressed circRNAs were searched out. The circRNA in pleural metastatic lung cancer showed a greater than 1.5-fold and P≤ 0. 05 compared with pleural tuberculosis was regarded as differentially expressed circRNA and then confirmed by qRT-PCR. After these circRNAs screening according to the principle of higher fold change and better consistency and their putatively targeting miRNAs prediction by bioinformatics software combined with literature review,the circRNAs that potentially contribute to lung cancer development and metastasis were preliminarily identified. Results The circRNA expression profile in pleural metastatic lung cancer showed remarkable changes compared with pleural tuberculosis. In pleural metastatic lung cancer,a total of 3 circRNAs showed a greater than 1. 5-fold change,and of them,2 were up-regulated and 1 were down-regulated. The significantly up-regulated circRNA hsa-circ-103 212( 1. 671 fold,P = 0. 0245) and hsa-circ-104 822( 1. 514 fold,P = 0.0478),and significantly down-regulated circRNA hsa-circ-100548( 1.808 fold,P = 0.0287) were obtained after screening. Bioinformatics analysis and literature review suggested that hsa-miR-613 and hsa-miR-24-3 p was potentially regulated by hsa-circ-104 822 which contributed to the metastasis and development of lung cancer. Conclusion The circRNA expression profile in pleural metastasis lung cancer is greatly changed. hsacirc-104 822 may play important roles in the metastasis and development of lung cancer.