Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou, Zhejiang, China.
Clin Chim Acta. 2017 Oct;473:237-244. doi: 10.1016/j.cca.2017.07.008. Epub 2017 Jul 8.
In this study, we investigated the differential expression of microRNAs in an ovarian cancer cell line HO-8910PM with increased migration and invasiveness activities. miR-1 was found to be one of the microRNA species most significantly downregulated in HO-8910PM compared with the control cell line HO-8910. We demonstrated that ovarian cancer tissues expressed decreased levels of miR-1 compared to non-neoplastic tissues. In vitro experiments showed that overexpression of miR-1 in HO-8910PM led to an inhibition of cell proliferation, blocking of cell cycle progression by G1 phase arrest, and decreased migration and invasiveness of HO-8910PM cells. Moreover, we confirmed that the expression of c-Met, a potential target of miR-1, was significantly inhibited following overexpression of miR-1 in HO-8910PM cells. Further analyses indicated that expression of factors including p-Akt, p-ERK1/2, CDK4, and p-Rb in HO-8910PM cells were affected by manipulation of c-Met expression. Infection of HO-8910PM cells with lentivirus vector expressing miR-1 led to a significant inhibition of tumor growth in the tumor subcutaneous nude mouse model. Taken together, these results indicated that miR-1 is downregulated in ovarian cancer tissues, and may play a tumor suppressive role by inhibiting c-Met expression and its effects on the regulation of cell proliferation, migration and invasion.
在这项研究中,我们研究了具有更高迁移和侵袭活性的卵巢癌细胞系 HO-8910PM 中 microRNAs 的差异表达。与对照细胞系 HO-8910 相比,miR-1 是 HO-8910PM 中下调最显著的 microRNA 之一。我们证明与非肿瘤组织相比,卵巢癌组织中 miR-1 的表达水平降低。体外实验表明,在 HO-8910PM 中过表达 miR-1 导致细胞增殖受到抑制,通过 G1 期阻滞阻断细胞周期进程,并降低 HO-8910PM 细胞的迁移和侵袭能力。此外,我们证实 c-Met 的表达,miR-1 的潜在靶标,在 HO-8910PM 细胞中过表达 miR-1 后显著受到抑制。进一步的分析表明,HO-8910PM 细胞中 c-Met 表达的操纵影响包括 p-Akt、p-ERK1/2、CDK4 和 p-Rb 在内的多种因子的表达。用表达 miR-1 的慢病毒载体感染 HO-8910PM 细胞导致肿瘤皮下裸鼠模型中肿瘤生长受到显著抑制。总之,这些结果表明 miR-1 在卵巢癌组织中下调,可能通过抑制 c-Met 表达及其对细胞增殖、迁移和侵袭的调节作用发挥肿瘤抑制作用。