Xu Dongkui, Liu Shikai, Zhang Liang, Song Lili
Department of Obstetrics & Gynaecology, Cangzhou Central Hospital, Hebei, 061001, China.
Department of Obstetrics & Gynaecology, Cangzhou Central Hospital, Hebei, 061001, China.
Biochem Biophys Res Commun. 2017 Apr 1;485(2):556-562. doi: 10.1016/j.bbrc.2016.12.020. Epub 2016 Dec 5.
The dysregulated molecules and their involvement in lymph node metastases of cervical cancer are far from been fully revealed. In this study, by reviewing MUC4 expression in The Human Protein Atlas and retrieving gene microarray data in GEO dataset (No. GDS4664), we found that MUC4 upregulation is associated with lymph node metastasis in cervical cancer. Knockdown of MUC4 in Hela and SiHa cells significantly reduced their invasion and also reduced the mesenchymal properties. By performing bioinformatics analysis, we observed that miR-211 is a potential suppressor of MUC4, which has a predicted highly conserved binding site in the 3'UTR of MUC among mammals. The following assays confirmed that miR-211 can directly target the 3'UTR of MUC4 and inhibit its expression at both mRNA and protein levels. In addition, enforced miR-211 expression phenocopies the effects of MUC4 siRNA in inhibiting cervical cancer cell invasion and reversing EMT properties. Therefore, we infer that miR-211 is a novel miRNA with suppressive effect on MUC4 expression and can inhibit cervical cancer cell invasion and EMT.
宫颈癌中失调的分子及其在淋巴结转移中的作用尚未完全揭示。在本研究中，通过查阅人类蛋白质图谱中MUC4的表达情况并检索GEO数据集（编号GDS4664）中的基因芯片数据，我们发现MUC4上调与宫颈癌淋巴结转移相关。在Hela和SiHa细胞中敲低MUC4可显著降低其侵袭能力，并降低间充质特性。通过生物信息学分析，我们观察到miR-211是MUC4的潜在抑制因子，在哺乳动物MUC的3'UTR中有一个预测的高度保守结合位点。以下实验证实miR-211可直接靶向MUC4的3'UTR并在mRNA和蛋白质水平抑制其表达。此外，强制表达miR-211可模拟MUC4 siRNA抑制宫颈癌细胞侵袭和逆转EMT特性的作用。因此，我们推断miR-211是一种对MUC4表达具有抑制作用的新型miRNA，可抑制宫颈癌细胞侵袭和EMT。
