胸膜转移性肺癌环状RNA表达谱及其临床意义

doi:10.3877/cma.j.issn.1674-6902.2017.06.009

中华肺部疾病杂志(电子版) ›› 2017, Vol. 10 ›› Issue (06) : 677 -680. doi: 10.3877/cma.j.issn.1674-6902.2017.06.009

所属专题：文献；

论著

胸膜转移性肺癌环状RNA表达谱及其临床意义

赵云峰¹, 张明周², 游雅婷², 钱澜兰², 郭亮², 吴学玲³^,^†(

)

^1. 200125　上海，上海市浦东新区浦南医院呼吸内科
^2. 400037　重庆，第三军医大学新桥医院呼吸内科
^3. 200025　上海，上海交通大学医学院仁济医院呼吸内科

收稿日期:2017-04-21 出版日期:2017-12-20
通信作者: 吴学玲
基金资助:
上海市卫生和计划生育委员会课题(201640377); 上海市浦东新区卫生系统重点专科培养计划资助(PWZ zk2017-18)

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

Yunfeng Zhao¹, Mingzhou Zhang², Yating You², Lanlan Qian², Liang Guo², Xueling Wu³^,^†()

^1. Department of Respiratory Medicine, Punan Hospital, Shanghai 200125, China
^2. Department of Respiratory Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing 400037 China
^3. Department of Respiratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025 China

Received:2017-04-21 Published:2017-12-20
Corresponding author: Xueling Wu
About author:
Corresponding author: Wu Xueling, Email: wu261912@126.com

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引用本文：

赵云峰, 张明周, 游雅婷, 钱澜兰, 郭亮, 吴学玲. 胸膜转移性肺癌环状RNA表达谱及其临床意义[J]. 中华肺部疾病杂志(电子版), 2017, 10(06): 677-680.

Yunfeng Zhao, Mingzhou Zhang, Yating You, Lanlan Qian, Liang Guo, Xueling Wu. Differentially expressed circular RNAs in human pleural metastatic lung cancer and clinical significance[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2017, 10(06): 677-680.

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。

关键词: 环状RNA, miRNA, 肺癌, 转移

Objective

To analyze the difference of circular RNA (circRNA) expression profiles between pleural metastatic lung cancer and pleural tuberculosis.

Methods

The circRNA expression profiles in 3 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-24-3p 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. hsa-circ-104 822 may play important roles in the metastasis and development of lung cancer.

Key words: Circular RNA, miRNA, Lung cancer, Metastasis

图1 circRNA火山图

图2 差异circRNA聚类图

表1 差异表达的circRNA

变　量	变化倍数	调节方向	circRNA	P值
ASCRP 003510	1.6712	上调	hsa_circRNA_103212	0.0245
ASCRP 005071	1.5135	上调	hsa_circRNA_104822	0.0478
ASCRP 000928	1.8085	下调	hsa_circRNA_100548	0.0287

表1 差异表达的circRNA

变　量	变化倍数	调节方向	circRNA	P值
ASCRP 003510	1.6712	上调	hsa_circRNA_103212	0.0245
ASCRP 005071	1.5135	上调	hsa_circRNA_104822	0.0478
ASCRP 000928	1.8085	下调	hsa_circRNA_100548	0.0287

表2 Arraystar预测的可能与circRNA相互作用的miRNA

circRNA	可能与circRNA相互作用的miRNA
hsa_cirRNA_103212	hsa-miR-494-5p、hsa-miR-135b-5p、hsa-miR-135a-5p、hsa-miR-410-5p、hsa-miR-518c-5p
hsa_cirRNA_104822	hsa-miR-613、hsa-miR-762、hsa-miR-766-5p、hsa-miR-24-3p、hsa-miR-1-3p
hsa_cirRNA_100548	hsa-miR-670-3p、hsa-miR-376-5p、hsa-miR-141-5p、hsa-miR-335-3p、hsa-miR-597-3p

表2 Arraystar预测的可能与circRNA相互作用的miRNA

circRNA	可能与circRNA相互作用的miRNA
hsa_cirRNA_103212	hsa-miR-494-5p、hsa-miR-135b-5p、hsa-miR-135a-5p、hsa-miR-410-5p、hsa-miR-518c-5p
hsa_cirRNA_104822	hsa-miR-613、hsa-miR-762、hsa-miR-766-5p、hsa-miR-24-3p、hsa-miR-1-3p
hsa_cirRNA_100548	hsa-miR-670-3p、hsa-miR-376-5p、hsa-miR-141-5p、hsa-miR-335-3p、hsa-miR-597-3p

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

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