Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China.
Department of Imaging, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China.
Pathol Res Pract. 2020 Apr;216(4):152854. doi: 10.1016/j.prp.2020.152854. Epub 2020 Feb 5.
MiRNAs affect various biological pathways associated with the development, progression, clinical outcome and treatment response improvement in cervical cancer. This study was performed to evaluate the effects of miRNA 96 on cervical cancer and to clarify the mechanism. Vivo and vitro experiments were conducted in our trial. MiR-96 is upregulated in cervical cancer cell lines and cervical cancer tissues and is correlated with clinical features in cervical cancer patients. Overexpression of miR-96 enhances proliferation of cervical cancer cells, while inhibiting miR-96 reduces the proliferation of cervical cancer cells. Inhibition of miR-96 significantly decreased the percentage of cells in the S phase and increased the percentage of cells in G1/G0 peak in both SiHa and CaSki cells compared with NC cells and decreased the expressions of p21, p27 and cyclin D1. FOXO1 3'-UTR was sub cloned into a luciferase reporter vector and the putative miR-96 binding site in the FOXO1 3'-UTR was mutated. Treated with miR-96 inhibitor consistently enhanced the luciferase activity of the FOXO1 3'-UTR luciferase reporter plasmids in both SiHa and CaSki cells, whereas mutations in the miR-96-binding site abolished the effect. Vivo experiment also support these results. Therefore, inhibition of miR-96 might suppress growth, proliferation of CC cells and promote apoptosis of CC cells both in vitro and in vivo.
miRNAs 影响与宫颈癌的发展、进展、临床结局和治疗反应改善相关的各种生物学途径。本研究旨在评估 miRNA96 对宫颈癌的影响，并阐明其机制。我们的试验进行了体内和体外实验。miR-96 在宫颈癌细胞系和宫颈癌组织中上调，并与宫颈癌患者的临床特征相关。miR-96 的过表达增强了宫颈癌细胞的增殖，而抑制 miR-96 则降低了宫颈癌细胞的增殖。与 NC 细胞相比，抑制 miR-96 显著降低了 SiHa 和 CaSki 细胞中 S 期细胞的百分比，并增加了 G1/G0 峰的百分比，同时降低了 p21、p27 和 cyclin D1 的表达。FOXO1 3'-UTR 被亚克隆到荧光素酶报告载体中，FOXO1 3'-UTR 中的假定 miR-96 结合位点发生突变。用 miR-96 抑制剂处理后，FOXO1 3'-UTR 荧光素酶报告质粒的荧光素酶活性在 SiHa 和 CaSki 细胞中均得到增强，而 miR-96 结合位点的突变则消除了这种作用。体内实验也支持这些结果。因此，抑制 miR-96 可能会抑制 CC 细胞的生长、增殖，并促进 CC 细胞的凋亡，无论是在体外还是体内。
