Comprehensive ceRNA network analysis and experimental studies identify an IGF2-AS/miR-150/IGF2 regulatory axis in colorectal cancer
Comprehensive ceRNA network analysis and experimental studies identify an IGF2-AS/miR-150/IGF2 regulatory axis in colorectal cancer
复制标题
全面的 ceRNA 网络分析和实验研究确定了结直肠癌中的 IGF2-AS/miR-150/IGF2 调节轴
DOI：
10.1016/j.prp.2020.153104
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发表时间：
2020-10-01
影响因子：
2.8
通讯作者：
Huang, Zhaohui
中科院分区：
文献类型：
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作者：
Liu, Bingxin;Liu, Yuhang;Huang, Zhaohui
近年来，越来越多的研究表明，长链非编码RNA（lncRNA）可作为microRNA（miRNA）海绵调控蛋白质编码基因的表达，在肿瘤的发生和发展中发挥重要作用。在本研究中，我们构建了一个竞争性内源性RNA（ceRNA）网络，并通过生物信息和实验验证确定了大肠癌（CRC）中潜在的调控轴。首先，我们分别从肿瘤基因组图谱（TCGA）数据库和江南大学附属医院结直肠癌患者数据库中检索结直肠癌的RNA表达谱，获得差异表达的lncRNA、miRNAs和mRNAs。建立了包括23个lncRNA、7个miRNAs和244个mRNAs的大肠癌ceRNA调控网络。为了进一步确定这些lncRNA-miRNA-mRNA调控轴可能在CRC肿瘤发生和预后中发挥重要作用，我们使用综合生物信息学方法进行了额外的分析。从该网络中获得了几个ceRNA调控轴，其由2个lncRNA、2个miRNA和5个mRNA组成。最后，通过对CRC细胞系和临床肿瘤组织的实验验证了这些ceRNA网络之间的相互作用和相关性，并确定了完全符合ceRNA理论的潜在IGF 2-AS/miR-150/IGF 2轴。根据qRT-PCR结果，miR-150过表达显著降低IGF 2-AS和IGF 2表达。结直肠癌组织中IGF 2-AS的表达与IGF 2的表达呈正相关。此外，双荧光素酶报告基因检测表明miR-150可与IGF 2-AS和IGF 2的3 'UTR结合。总之，构建的IGF 2-AS/miR-150/IGF 2网络可能为结直肠癌的发生发展提供了潜在的机制，并有望成为结直肠癌治疗的新靶点。
Recently, a growing body of studies has demonstrated that long non-coding RNA (lncRNA) can act as microRNA (miRNA) sponges to regulate protein-coding gene expression and play essential roles in tumor initiation and progression. In the present study, we constructed a competitive endogenous RNA (ceRNA) network and identified potential regulatory axes in colorectal cancer (CRC) through both bioinformation and experimental validation. Firstly, we obtained differentially expressed (DE) lncRNAs, miRNAs, and mRNAs by analyzing the RNA expression profiles of CRC retrieved from The Cancer Genome Atlas (TCGA) database and CRC patients' data from affiliated Hospital of Jiangnan University, respectively. Then, we established a ceRNA regulatory network of CRC that includes 23 lncRNAs, 7 miRNAs and 244 mRNAs. To further identify these lncRNA-miRNA-mRNA regulatory axes which might play vital roles in CRC tumorigenesis and prognosis, we performed additional analyses using comprehensive bioinformatic methods. Several ceRNA regulatory axes, which consist of 2 lncRNAs, 2 miRNAs and 5 mRNAs, were obtained from the network. Finally, the interactions and correlations among these ceRNA networks were validated by experiments on CRC cell lines and clinical tumor tissues, and a potential IGF2-AS/miR-150/IGF2 axis that perfectly conform to the ceRNA theory was determined. According to the qRT-PCR results, miR-150 overexpression remarkably decreased IGF2-AS and IGF2 expression. Meanwhile, IGF2-AS expression was positively correlated with IGF2 expression in tumor tissue of CRC patients. Besides, dual luciferase reporter assays indicated that miR-150 could bound to IGF2-AS and the 3'UTR of and IGF2. In general, the constructed novel IGF2-AS/miR-150/IGF2 network might provide potential mechanisms of CRC development, and could act as a promising target for CRC treatment.