Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, 150020, China.
Department of Biostatistics, Public Health School, Harbin Medical University, Harbin, 150081, China.
J Biochem Mol Toxicol. 2018 Aug;32(8):e22168. doi: 10.1002/jbt.22168. Epub 2018 Jul 13.
Based on miR-874 expression levels in the GSE47841 microarray, we hypothesized that the mature products of miR-874, miR-874-3p, or miR-874-5p, would inhibit epithelial ovarian cancer (EOC) cell proliferation, metastasis, and chemoresistance. We first examined miR-874-3p and miR-874-5p expression levels in primary EOC tumor tissue samples and found that they were significantly decreased. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell proliferation and transwell assays revealed that miR-874-3p and miR-874-5p significantly inhibit EOC cell proliferation, migration, and invasion. Then, using MTT and soft agar assays of paclitaxel-treated Caov3 and SKOV3 cells transfected with miR-874-3p and miR-874-5p, we found that miR-874-3p and miR-874-5p enhance EOC cell chemosensitivity. We then confirmed that serine/threonine-protein kinase 2 (SIK2) was a target gene of miR-874-3p and miR-874-5p. Overall, the results of this study indicate that SIK2 expression can serve as a prognostic biomarker for EOC and that miR-874-3p and miR-874-5p have the potential to enhance clinical treatment of EOC.
基于 miR-874 在 GSE47841 芯片中的表达水平，我们假设 miR-874 的成熟产物，miR-874-3p 或 miR-874-5p，将抑制上皮性卵巢癌（EOC）细胞的增殖、转移和化疗耐药性。我们首先检测了原发性 EOC 肿瘤组织样本中 miR-874-3p 和 miR-874-5p 的表达水平，发现它们显著降低。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）细胞增殖和 Transwell 分析表明，miR-874-3p 和 miR-874-5p 显著抑制 EOC 细胞的增殖、迁移和侵袭。然后，通过 MTT 和软琼脂实验检测紫杉醇处理后转染 miR-874-3p 和 miR-874-5p 的 Caov3 和 SKOV3 细胞，我们发现 miR-874-3p 和 miR-874-5p 增强了 EOC 细胞的化疗敏感性。我们随后证实丝氨酸/苏氨酸蛋白激酶 2（SIK2）是 miR-874-3p 和 miR-874-5p 的靶基因。总的来说，这项研究的结果表明，SIK2 表达可以作为 EOC 的预后生物标志物，miR-874-3p 和 miR-874-5p 有可能增强 EOC 的临床治疗效果。
