Wang Tingfeng, Feng Juan, Zhang Aiyun
Department of Gynaecology and Obstetrics, Weifang Maternity and Child Care Hospital, Weifang, Shandong 261042, P.R. China.
Department of Gynaecology and Obstetrics, AnQiu Maternity and Child Care Hospital, Weifang, Shandong 261042, P.R. China.
Exp Ther Med. 2020 Mar;19(3):2059-2066. doi: 10.3892/etm.2020.8449. Epub 2020 Jan 14.
Cervical cancer is the most l malignancy amongst women worldwide. MicroRNAs (miRNAs/miRs) play a critical role in the progression of cervical cancer. Compelling evidence indicates that miR-584 acts as a tumor suppressor in some types of cancers. However, the function of miR-584 in cervical cancer has not been illustrated. In the present study, the effects and mechanism of miR-584 in the process of proliferation, migration and invasion, and drug sensitivity to cisplatin in cervical cancer were determined. miR-584 expression decreased markedly in cervical cancer tissues and cell lines compared with healthy control samples. Dual-luciferase reporter assays confirmed that glioma-associated oncogene 1 (GLI1) is a novel molecular target of miR-584. The overexpression of miR-584 inhibited the expression of GLI1, reduced cell proliferation, migration and invasion, and induced apoptosis in HeLa cells. However, the silencing of miR-584 in CaSki cells produced the opposite effects. In addition, the overexpression of GLI1 in HeLa-cells overexpressing miR-584 markedly reversed the miR-584-induced inhibitory effect. Flow cytometry results showed that miR-584 enhanced cisplatin sensitivity by promoting chemotherapy-induced apoptosis. Therefore, miR-584 acted as a tumor suppressor miRNA and might be a novel target gene for future cervical cancer treatments.
宫颈癌是全球女性中最常见的恶性肿瘤。微小RNA（miRNAs/miRs）在宫颈癌的进展中起着关键作用。有力证据表明，miR-584在某些类型的癌症中作为肿瘤抑制因子发挥作用。然而，miR-584在宫颈癌中的功能尚未阐明。在本研究中，确定了miR-584在宫颈癌增殖、迁移和侵袭过程以及对顺铂的药物敏感性方面的作用和机制。与健康对照样本相比，miR-584在宫颈癌组织和细胞系中的表达明显降低。双荧光素酶报告基因检测证实，胶质瘤相关致癌基因1（GLI1）是miR-584的一个新分子靶点。miR-584的过表达抑制了GLI1的表达，降低了细胞增殖、迁移和侵袭，并诱导了HeLa细胞凋亡。然而，在CaSki细胞中沉默miR-584产生了相反的效果。此外，在过表达miR-584的HeLa细胞中过表达GLI1明显逆转了miR-584诱导的抑制作用。流式细胞术结果表明，miR-584通过促进化疗诱导的凋亡增强了顺铂敏感性。因此，miR-584作为一种肿瘤抑制性miRNA，可能是未来宫颈癌治疗的一个新靶点基因。
