Circ-ITGA7 sponges miR-3187-3p to upregulate ASXL1, suppressing colorectal cancer proliferation
Circ-ITGA7 sponges miR-3187-3p to upregulate ASXL1, suppressing colorectal cancer proliferation
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DOI：
10.2147/cmar.s203137
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Ma, Jinping
中科院分区：
文献类型：
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作者：
Yang, Guangpu;Zhang, Tianhao;Ma, Jinping
背景资料：作为一类内源性非编码RNA，近年来研究发现，某些环状RNA（circular RNA，circRNA）在大肠癌（colorectal cancer，CRC）的发生、发展过程中起重要调控作用。然而，大多数这些circRNA的功能在CRC.Purpose：本研究的目的是确定circRNA-ITGA 7在CRC细胞proliferation.Patients和方法中的作用机制仍不清楚：人类全基因组circRNA微阵列V2分析用于表达谱分析。利用TargetScan、miRDB、miRTarbase和miRMap等在线生物信息学数据库对靶基因进行预测。使用细胞转染建立基因过表达和沉默细胞模型。进行qRT-PCR和蛋白质印迹以评估基因和蛋白质表达。CCK 8、集落形成和细胞周期分析用于增殖测试。结果：CircRNA测序结果显示，与癌旁正常组织相比，CRC中新的circRNA circ-ITGA 7的表达明显降低。功能获得研究进一步证明了circ-ITGA 7抑制CRC细胞的增殖。基于预测和验证，我们随后发现miR-3187- 3 p是一种circ-ITGA 7相关的miRNA。结论：Circ-ITGA 7可能通过吸收miR-3187- 3 p和增加ASXL 1的表达来抑制CRC的增殖。因此，circ-ITGA 7可能是CRC的潜在诊断生物标志物和治疗靶点。
Background: As a class of endogenous noncoding RNAs, some circular RNAs (circRNAs) have recently been reported to play a role in the regulation of tumorigenesis and progression in colorectal cancer (CRC). However, the mechanisms by which most these circRNAs function in CRC are still unclear.Purpose: The objective of this study was to identify the role of circRNA-ITGA7 in CRC cell proliferation.Patients and methods: Human genome-wide circRNA microarray v2 analysis was used for expression profile analysis. Target genes were predicted using online bioinformatics database, including TargetScan, miRDB, miRTarbase and miRMap. Gene overexpression and silencing cell models were built using cell transfection. qRT-PCR and Western blot were performed for gene and protein expression assessment. CCK8, colony formation and cell cycle analysis were used for proliferation testing. Annexin V-FITC analysis was performed for apoptosis detection.Results: CircRNA sequencing analysis suggested that compared to that in adjacent normal control tissue, the expression of circ-ITGA7, a novel circRNA, is decreased significantly in CRC. Gain-of-function studies further demonstrated that circ-ITGA7 suppressed proliferation of CRC cells. Based on prediction and verification, we subsequently revealed that miR-3187-3p is a circ-ITGA7-associated miRNA. Furthermore, RNA sequencing and bioinformatics analyses showed that ASXL1-5'UTR, the target of miR-3187-3p, is upregulated in circ-ITGA7-overexpressed cells and mediates the circ-ITGA7-induced suppression of proliferation.Conclusion: Circ-ITGA7 might suppress CRC proliferation by sponging miR-3187-3p and increasing ASXL1 expression. Thus, circ-ITGA7 might be a potential diagnostic biomarker and a therapeutic target for CRC.