Tumor-suppressive miR-26a and miR-26b inhibit cell aggressiveness by regulating FUT4 in colorectal cancer.
Tumor-suppressive miR-26a and miR-26b inhibit cell aggressiveness by regulating FUT4 in colorectal cancer.
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DOI：
10.1038/cddis.2017.281
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发表时间：
2017-06-22
影响因子：
9
通讯作者：
Jia L
中科院分区：
文献类型：
--
作者：
Li Y;Sun Z;Liu B;Shan Y;Zhao L;Jia L
转移是一个多步骤的分子网络过程，是结直肠癌（CRC）患者死亡的主要原因。 MicroRNA (miRNA) 作为抑癌基因或癌基因在肿瘤发生中发挥着关键作用。据报道，岩藻糖基转移酶 4 (FUT4) 表达的增加与结直肠癌的侵袭和转移特性有关。为了识别结直肠癌 (CRC) 的潜在关键 miRNA 及其靶基因，我们比较了转移性 CRC 细胞 SW620 和原发性 CRC 细胞 SW480 之间的 miRNA 表达谱。微阵列分析显示，与具有低转移潜力的SW480细胞相比，具有高转移潜力的SW620细胞中有85个差异表达的miRNA。 miR-26a和miR-26b在SW620细胞中的表达低于SW480细胞，并且在结直肠癌患者的肿瘤组织中表达低于癌旁正常组织。通过应用生物信息学方法预测靶向FUT4 3'-UTR的miRNA，我们将FUT4确定为miR-26a/26b靶向基因之一，而该靶基因在结直肠癌细胞系、肿瘤组织和相应的邻近组织中表现出与miR-26a/26b相反的表达模式。强制miR-26a/26b表达影响CRC细胞的迁移行为和FUT4表达，而CRC细胞系中FUT4表达的改变调节miR-26a/26b模拟物或抑制剂转染后的进展。 FUT4 还直接调节 SW620 和 SW480 细胞的攻击性。此外，统计分析显示，低 miR-26a/26b 水平和高 FUT4 表达与较差的总生存率呈正相关。已鉴定的 CRC 限制性 miR-26a 和 miR-26b 可能通过其靶基因 FUT4 参与癌症进展，表明它们在 CRC 治疗中的潜在用途。
Metastasis is a multistep molecular network process, which is the major cause of death in patients with colorectal cancer (CRC). MicroRNAs (miRNAs) play pivotal roles in tumorigenesis as either tumor suppressors or oncogenes. Increased expression of fucosyltransferase4 (FUT4) has been reported to be associated with the invasive and metastatic properties of CRC. Here to identify potential key miRNAs and their target genes for colorectal cancer (CRC), we compared miRNA expression profiles between metastatic CRC cell SW620 and primary CRC cell SW480. Microarray analysis revealed that there were 85 differentially expressed miRNAs in SW620 cells with highly metastatic potential compared to SW480 cells with lowly metastatic potential. The expression of miR-26a and miR-26b were lower in SW620 cells than in SW480 cells, as well as downregulated in tumor tissues than in adjacent normal tissues of CRC patients. By applying bioinformatic approaches for the prediction of miRNA targeting 3′-UTR of FUT4, we identified FUT4 as one of the miR-26a/26b-targeted genes, while the expression of the target gene exhibited patterns opposite to that of miR-26a/26b in CRC cell lines, tumor tissues and corresponding adjacent tissues. Forced miR-26a/26b expression affected migratory behavior of CRC cells and FUT4 expression, while altered expression of FUT4 in CRC cell lines modulated progression upon transfection with miR-26a/26b mimic or inhibiter. FUT4 also regulated directly aggressiveness of SW620 and SW480 cells. Moreover, statistical analyses revealed that low miR-26a/26b levels and high expression of FUT4 were positively correlated with poor overall survival. The identified CRC-restricted miR-26a and miR-26b might be implicated in cancer progression via their target gene FUT4, suggesting their potential usage in CRC treatment.
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影响因子：
4.6
作者：
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通讯作者：
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作者：
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