Whole-transcriptome analysis reveals a potential hsa_circ_0001955/hsa_circ_0000977-mediated miRNA-mRNA regulatory sub-network in colorectal cancer
Whole-transcriptome analysis reveals a potential hsa_circ_0001955/hsa_circ_0000977-mediated miRNA-mRNA regulatory sub-network in colorectal cancer
复制标题
全转录组分析揭示结直肠癌中潜在的 hsa_circ_0001955/hsa_circ_0000977 介导的 miRNA-mRNA 调节子网络
DOI：
10.18632/aging.102945
复制
发表时间：
2020-03-31
期刊：
影响因子：
5.2
通讯作者：
Lou, Weiyang
中科院分区：
文献类型：
--
作者：
Ding, Bisha;Yao, Minya;Lou, Weiyang
工作背景：环状RNA（circular RNA，circRNA）是一类新型的非编码RNA，具有海绵状的微小RNA（microRNA，miRNA）结构，在生物学过程和致病机制中发挥重要作用。然而，关于结直肠癌（CRC）中circRNA的研究仍然不足。结果：通过差异表达分析，筛选出10个候选circRNA（6个上调，4个下调）。10个circRNA中有9个在CSCD上可用，它们的结构显示了miRNA的结合潜力。交叉分析显示，miR-145- 5 p、miR-3127- 5 p、miR-761、miR-4766- 3 p、miR-135 a-5 p、miR-135 b-5 p、miR-374 a-3 p和miR-330- 3 p是8种与circRNA结合能力最强的miRNAs。进一步的表达验证和相关性分析表明hsa_circ_0001955/miR-145- 5 p和hsa_circ_0000977/miR-135 b-5 p轴是CRC中的关键通路。随后，通过靶基因预测、差异表达分析、交叉分析和相关性分析，发现CDK 6、MMP 12和RAB 3 IP是hsa_circ_0001955/miR-145- 5 p轴的三个潜在下游靶点，FOXO 1、MBNL 1、MEF 2C、RECK、PPM 1 E、TTLL 7和PCP 4L 1是CRC中hsa_circ_0000977/miR-135 b-5 p轴的7个潜在下游靶点。最后，我们还证实了hsa_circ_0001955或hsa_circ_0000977的表达与其在CRC中的各自靶点呈显着正相关。结论：在本研究中，我们通过一系列的计算机分析和实验验证，构建了一个潜在的hsa_circ_0001955/hsa_circ_0000977介导的CRC中circRNA-miRNA-mRNA调控网络。方法：从GEO获得CRC和匹配的正常样本的全转录组微阵列。CSCD鉴定了circRNA的结构。利用starBase和miRNet分别对circRNA的miRNA和miRNA的靶基因进行了预测。使用GEO和TCGA数据评估RNA-RNA相互作用之间的表达相关性。最后，基于竞争性内源RNA（ceRNA）假说，构建了一个潜在的circRNA-miRNA-mRNA网络。
Background: Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been found to act as microRNA (miRNA) sponges and thus play key roles in biological processes and pathogenesis. However, studies regarding circRNAs in colorectal cancer (CRC) remain inadequate. Results: By differential expression analysis, 10 candidate circRNAs (6 upregulated and 4 downregulated circRNAs) were chosen. 9 of 10 circRNAs were available on CSCD and their structure showed the binding potential of miRNA. Intersection analysis revealed that miR-145-5p, miR-3127-5p, miR-761, miR-4766-3p, miR-135a-5p, miR-135b-5p, miR-374a-3p and miR-330-3p were 8 miRNAs with the most potential in binding circRNAs. Further expression validation and correlation analysis demonstrated hsa_circ_0001955/miR-145-5p and hsa_circ_0000977/miR-135b-5p axes as key pathways in CRC. Subsequently, target gene prediction, differential expression analysis, intersection analysis and correlation analysis showed that CDK6, MMP12 and RAB3IP were the three potential downstream targets of hsa_circ_0001955/miR-145-5p axis and FOXO1, MBNL1, MEF2C, RECK, PPM1E, TTLL7 and PCP4L1 were the seven potential downstream targets of hsa_circ_0000977/miR-135b-5p axis in CRC. Finally, we also confirmed that expression of hsa_circ_0001955 or hsa_circ_0000977 was significantly positively correlated with their individual targets in CRC. Conclusions: In the present work, we constructed a potential hsa_circ_0001955/hsa_circ_0000977-mediated circRNA-miRNA-mRNA regulatory network in CRC by a series of in silico analysis and experimental validation. Methods: Whole-transcriptome microarrays from CRC and matched normal samples were obtained from GEO. The structure of circRNA was identified by CSCD. starBase and miRNet were successively used to predict miRNA of circRNA and target gene of miRNA. Expression correlation between RNA-RNA interactions was assessed using GEO and TCGA data. Finally, a potential circRNA-miRNA-mRNA network was established based on competing endogenous RNA (ceRNA) hypothesis.