MicroRNA-126 functions as a tumor suppressor in colorectal cancer cells by targeting CXCR4 via the AKT and ERK1/2 signaling pathways
MicroRNA-126 functions as a tumor suppressor in colorectal cancer cells by targeting CXCR4 via the AKT and ERK1/2 signaling pathways
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MicroRNA-126 通过 AKT 和 ERK1/2 信号通路靶向 CXCR4，在结直肠癌细胞中发挥肿瘤抑制因子的作用
DOI：
10.3892/ijo.2013.2168
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发表时间：
2014-01-01
影响因子：
5.2
通讯作者：
Luo, Hesheng
中科院分区：
文献类型：
--
作者：
Liu, Yaling;Zhou, Yu;Luo, Hesheng
最近的证据表明，microRNA-126 （miR-126）表达的改变与结直肠癌（CRC）的进展有关。然而，miR-126在结直肠癌中的确切作用和机制尚不清楚。本研究的目的是探讨miR-126在结直肠癌细胞中的作用，并阐明miR-126在结直肠癌细胞中的介导机制。首先，使用qRT-PCR分析了miR-126在4种人CRC细胞系（SW480、SW620、HT-29和HCT-116）中的表达。此外，通过细胞计数试剂盒8、细胞周期、细胞凋亡和transwell实验检测miR-126在CRC细胞中的体外生物学特性。采用qRT-PCR、western blotting和荧光素酶报告基因法检测mir -126在结直肠癌细胞中介导的机制和途径。我们发现miR-126过表达抑制了CRC细胞的增殖、迁移和侵袭，并在G0/G1期诱导细胞停滞，这表明miR-126在CRC细胞中起肿瘤抑制作用。此外，我们发现CXC趋化因子受体4 （CXCR4）是miR-126的靶标，并发现它受到miR-126的负调控。我们证明mir -126介导的肿瘤抑制可能部分依赖于AKT和ERK1/2信号通路。总之，我们的数据显示miR-126通过AKT和ERK1/2信号通路调节CXCR4的表达，在结直肠癌细胞中发挥抑癌作用，可能成为结直肠癌治疗策略的新靶点。
Recent evidence shows that altered microRNA-126 (miR-126) expression is implicated in the progression of colorectal cancer (CRC). However, the precise roles and mechanisms of miR-126 in CRC remain unclear. The aim of this study was to investigate the roles of miR-126 in CRC cells and to elucidate miR-126-mediated mechanisms in CRC cells. First, miR-126 expression was analyzed using qRT-PCR in 4 human CRC cell lines (SW480, SW620, HT-29 and HCT-116). Furthermore, the biological properties of miR-126 in CRC cells in vitro were examined by applying Cell Counting Kit 8, cell cycle, cell apoptosis and transwell assays. The mechanisms and pathways of miR-126-mediated in CRC cells were detected by using qRT-PCR, western blotting and luciferase reporter assay. We found that miR-126 overexpression inhibited cell proliferation, migration and invasion, and induced cell arrest in the G0/G1 phase of CRC cells, suggesting that miR-126 functions as a tumor suppressor in CRC cells. Furthermore, we identified the CXC chemokine receptor 4 (CXCR4) as a target of miR-126, and showed that it was negatively regulated by miR-126. We demonstrated that miR-126-mediated tumor suppression might be partly dependent on AKT and ERK1/2 signaling pathways. In conclusion, our data revealed that miR-126 functions as a tumor suppressor in CRC cells by regulating CXCR4 expression via the AKT and ERK1/2 signaling pathways and might be a novel target for therapeutic strategies in CRC.