Wang Wei, He Ying, Rui Jing, Xu Mao-Qi
Department of General Surgery, Wuhu Hospital of Traditional Chinese Medicine, Wuhu, Anhui 241000, P.R. China.
Department of Stomatology, The Second People's Hospital of Wuhu, Wuhu, Anhui 241000, P.R. China.
Oncol Lett. 2019 Jan;17(1):807-814. doi: 10.3892/ol.2018.9710. Epub 2018 Nov 15.
Colorectal cancer (CRC) is a common malignancy with high morbidity. MicroRNAs (miRNAs or miRs) have been demonstrated to be critical post-transcriptional regulators in tumorigenesis. The current study aimed to investigate the effect of miR-410 on the proliferation and metastasis of CRC. The expression of miR-410 was examined in CRC cell lines. SW-480 and HCT-116 CRC cell lines were employed and transfected with miR-410 inhibitor or miR-410 mimics. The association between miR-410 and dickkopf-related protein 1 (DKK-1) was verified by luciferase reporter assay. Cell viability and apoptosis were detected by Cell Counting Kit-8 (CCK-8) and flow cytometry assay. Cell migration and invasion capacity were determined by Transwell assay. The protein level of DKK1, β-catenin and phosphorylated glycogen synthase kinase-3β (pGSK-3β) were analyzed by western blotting. miR-410 was revealed to be upregulated in CRC cell lines. Further studies identified DKK-1 as a direct target of miR-410. In addition, knockdown of miR-410 promoted the expression of DKK, inhibited CRC cell proliferation, migration and invasion capacity, and induced cell apoptosis, while overexpression of miR-410 reversed these results. miR-410 silencing also decreased β-catenin and pGSK-3β levels. The current study indicated that miR-410 negatively regulates the expression of DKK-1 . miR-410 promotes malignancy phenotypes in CRC cell lines. This regulatory effect of miR-410 may be associated with the Wnt/β-catenin signaling pathway. Therefore, miR-410 could be used as a biomarker for predicting the progression of CRC.
结直肠癌（CRC）是一种常见的高发病率恶性肿瘤。微小RNA（miRNA或miR）已被证明是肿瘤发生过程中关键的转录后调节因子。本研究旨在探讨miR-410对CRC增殖和转移的影响。检测了CRC细胞系中miR-410的表达。使用SW-480和HCT-116 CRC细胞系，并分别用miR-410抑制剂或miR-410模拟物进行转染。通过荧光素酶报告基因检测验证了miR-410与Dickkopf相关蛋白1（DKK-1）之间的关联。采用细胞计数试剂盒-8（CCK-8）和流式细胞术检测细胞活力和凋亡情况。通过Transwell检测确定细胞迁移和侵袭能力。采用蛋白质印迹法分析DKK1、β-连环蛋白和磷酸化糖原合酶激酶-3β（pGSK-3β）的蛋白水平。结果显示，CRC细胞系中miR-410表达上调。进一步研究确定DKK-1是miR-410的直接靶点。此外，敲低miR-410可促进DKK表达，抑制CRC细胞增殖、迁移和侵袭能力，并诱导细胞凋亡，而miR-410过表达则逆转了这些结果。miR-410沉默还降低了β-连环蛋白和pGSK-3β水平。本研究表明，miR-410负向调节DKK-1的表达。miR-410促进CRC细胞系中的恶性表型。miR-410的这种调节作用可能与Wnt/β-连环蛋白信号通路有关。因此，miR-410可作为预测CRC进展的生物标志物。
