miR-124 inhibits cell growth through targeting IQGAP1 in colorectal cancer
miR-124 inhibits cell growth through targeting IQGAP1 in colorectal cancer
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miR-124 通过靶向 IQGAP1 抑制结直肠癌细胞生长
DOI：
10.3892/mmr.2018.9518
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发表时间：
2018-12-01
影响因子：
3.4
通讯作者：
Zhang, Yu
中科院分区：
文献类型：
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作者：
Fan, Jianyu;Zhang, Wenjing;Zhang, Yu
MicroRNA (miRNA/miR)-124 是一种 miRNA，具有肿瘤抑制作用，但在肿瘤中经常缺失。尽管 miR-124 已被证实能够靶向信号转导子和转录激活子 3、叉头盒 Q1 和 Slug 等致癌基因，但 miR-124 与促进肿瘤进展的潜在靶基因之间的机制联系仍有待研究。含有 GTP 酶激活蛋白 1 (IQGAP1) 的 IQ 基序是一种支架蛋白，参与蛋白质-蛋白质相互作用并整合不同的信号通路。先前的研究表明，IQGAP1 的过度表达可增强丝裂原激活蛋白激酶 1 和 -catenin 信号级联的活性，从而促进肿瘤进展。本研究旨在确定 miR-124 和 IQGAP1 在结直肠癌 (CRC) 中的调节联系。结果表明，IQGAP1 在 CRC 组织和细胞系中异常过度表达。通过引入短发夹-IQGAP1慢病毒敲低IQGPA1可抑制CRC细胞生长和集落形成能力，同时抑制细胞外信号调节激酶（ERK）1/2的磷酸化和β-catenin表达。此外，还证明 miR-124 在 CRC 中被沉默。 CRC 细胞中 miR-124 的恢复阻碍了细胞生长和集落形成能力。使用荧光素酶报告基因测定证实了 miR-124 与 IQGAP1 mRNA 3 个非翻译区的直接结合。重要的是，在 miR-124 恢复细胞中观察到 IQGAP1 表达下调，同时磷酸化 -ERK1/2 和 -catenin 减少。总之，本研究描述了 CRC 进展中 miR-124/IQGAP1 联系的潜在机制。沉默 miR-124 可能会抑制 IQGAP1 表达，导致 ERK1/2 和 -catenin 信号传导活性增加。
MicroRNA (miRNA/miR)-124 is a miRNA, which exerts tumor suppressive effects but is frequently absent in tumors. Although it has been validated to target oncogenic genes such as signal transducer and activator of transcription 3, forkhead box Q1, and Slug, the mechanistic link between miR-124 and potential target genes that contribute to tumor progression, is yet to be investigated. IQ motif containing GTPase activating protein 1 (IQGAP1) is a scaffold protein that participates in protein-protein interactions and integrating diverse signaling pathways. Previous studies suggest that overexpression of IQGAP1 enhances activity of mitogen activated protein kinase 1 and -catenin signaling cascades to facilitate tumor progression. The present study aimed to identify the regulative link between miR-124 and IQGAP1 in colorectal cancer (CRC). It was demonstrated that IQGAP1 was aberrantly overexpressed in CRC tissues and cell lines. Knockdown of IQGPA1 by introducing short hairpin-IQGAP1 lentivirus inhibited CRC cell growth and colony formation ability, and simultaneously suppressed phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and -catenin expression. Furthermore, it was demonstrated that miR-124 was silenced in CRC. Restoration of miR-124 in CRC cells impeded cell growth and colony formation ability. The direct binding of miR-124 to the 3untranslated region of IQGAP1 mRNA was confirmed using a luciferase reporter gene assay. Importantly, downregulation of IQGAP1 expression was observed in miR-124-restoration cells with simultaneous reduction of phosphorylated-ERK1/2 and -catenin. In conclusion, the present study describes a potential mechanism underlying the miR-124/IQGAP1 link in CRC progression. Silencing of miR-124 may depress IQGAP1 expression, leading to increased activity of ERK1/2 and -catenin signaling.