Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Placenta. 2012 Oct;33(10):824-9. doi: 10.1016/j.placenta.2012.07.012. Epub 2012 Aug 1.
MiR-155 is known to participate in various cellular processes by targeting gene expression. We previously revealed a link between miR-155 and perturbation of trophoblast invasion and differentiation. This study aimed to investigate the target molecule(s) of miR-155 on the influence on the proliferation and migration of trophoblast cells. Bioinformatics analysis showed that, at the 3' untranslated region (UTR) of cyclin D1, six bases are complementary to the seed region of miR-155. Luciferase assays and cyclin D1 3'UTR transfection assays validated that cyclin D1 3'UTR was the target of miR-155 in HTR-8/SVneo cells. Overexpression of miR-155 in HTR-8/SVneo cells reduced the level of cyclin D1 protein, decreased cell proliferation and invasion, and increased cell number at the G1 stage. Furthermore, the increased expression of miR-155 also regulated the protein levels of kinase inhibitory protein p27 and phosphorylated cytoskeletal protein filamin A. In conclusion, we found that cyclin D1 may be a target of miR-155 in HTR-8/SVneo cells, and demonstrated a negative regulatory role of miR-155 involved in cyclin D1/p27 pathway in proliferation and migration of the cells.
miR-155 通过靶向基因表达参与各种细胞过程。我们之前揭示了 miR-155 与滋养细胞侵袭和分化失调之间的联系。本研究旨在探讨 miR-155 对滋养细胞增殖和迁移的影响的靶分子(s)。生物信息学分析表明,在 cyclin D1 的 3'非翻译区(UTR)中,有六个碱基与 miR-155 的种子区域互补。荧光素酶测定和 cyclin D1 3'UTR 转染测定验证了 cyclin D1 3'UTR 是 HTR-8/SVneo 细胞中 miR-155 的靶标。在 HTR-8/SVneo 细胞中过表达 miR-155 降低了 cyclin D1 蛋白水平,减少了细胞增殖和侵袭,并增加了 G1 期的细胞数量。此外,miR-155 的表达增加还调节了激酶抑制蛋白 p27 和磷酸化细胞骨架蛋白细丝蛋白 A 的蛋白水平。总之,我们发现 cyclin D1 可能是 HTR-8/SVneo 细胞中 miR-155 的靶标,并证明了 miR-155 在细胞增殖和迁移中涉及 cyclin D1/p27 途径的负调节作用。