Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, People's Republic of China.
Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, People's Republic of China.
Hum Cell. 2020 Jul;33(3):780-789. doi: 10.1007/s13577-020-00364-4. Epub 2020 May 14.
Emerging evidences have indicated that abnormal expression of microRNAs (miRNAs) contributed to carcinogenesis of ovarian cancer. However, the molecular mechanism of many aberrant expressed miRNAs was not known. Here, we discovered that miR-1224-5p was a downregulated miRNA in ovarian cancer via bioinformatic analysis and RT-qPCR. It was found that upregulation of miR-1224-5p inhibited cell proliferation and invasion ability of ovarian cancer cells. SND1, a well-characterized oncogene, was predicted as a target gene of miR-1224-5p. The western blotting, dual luciferase reporter assay, RNA-binding protein immunoprecipitation assay, and RT-qPCR demonstrated SND1 as a target gene of miR-1224-5p in ovarian cancer. MiR-1224-5p inhibited the expression of mesenchymal markers and increased the expression of epithelial markers in ovarian cancer cells via targeting SND1, indicating miR-1224-5p was involved in epithelial mesenchymal transition. The rescue assay manifested that miR-1224-5p-regulated cell proliferation and invasion mainly rely on downregulation of SND1 in ovarian cancer cells. In conclusion, our study revealed a direct regulatory association between miR-1224-5p and SND1 and their involvement in ovarian carcinogenesis.
已有研究表明，微小 RNA（miRNAs）的异常表达与卵巢癌的发生有关。然而，许多异常表达的 miRNA 的分子机制尚不清楚。在这里，我们通过生物信息学分析和 RT-qPCR 发现 miR-1224-5p 在卵巢癌中呈下调表达。研究发现，上调 miR-1224-5p 抑制了卵巢癌细胞的增殖和侵袭能力。SND1 是一种公认的癌基因，被预测为 miR-1224-5p 的靶基因。Western blot、双荧光素酶报告基因检测、RNA 结合蛋白免疫沉淀实验和 RT-qPCR 均证实 SND1 是卵巢癌细胞中 miR-1224-5p 的靶基因。miR-1224-5p 通过靶向 SND1 抑制了卵巢癌细胞中间充质标志物的表达，增加了上皮标志物的表达，表明 miR-1224-5p 参与了上皮间质转化。挽救实验表明，miR-1224-5p 调控卵巢癌细胞的增殖和侵袭主要依赖于 SND1 的下调。综上所述，本研究揭示了 miR-1224-5p 与 SND1 之间的直接调控关系及其在卵巢癌发生中的作用。
