MicroRNA-877 is downregulated in cervical cancer and directly targets MACC1 to inhibit cell proliferation and invasion

被引:24
|
作者
Meng, Fanxu [1 ]
Ou, Jian [1 ]
Liu, Jinyu [1 ]
Li, Xindi [1 ]
Meng, Yanli [1 ]
Yan, Ling [1 ]
Deng, Ping [1 ]
Sun, Baosheng [1 ]
机构
[1] Jilin Canc Hosp, Dept Radiotherapy, 1018 Huguang Rd, Changchun 130012, Jilin, Peoples R China
关键词
microRNA-877; cervical cancer; proliferation; invasion; metastasis-associated in colon cancer-1; COLON CANCER-1; METASTASIS; CARCINOMA; EXPRESSION; GROWTH; PROGNOSIS; RISK;
D O I
10.3892/etm.2019.7989
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Previously, a number of microRNAs (miRNAs) have been reported to be dysregulated in cervical cancer, and dysregulated miRNAs may play crucial roles in the development and progression of cervical cancer. Hence, investigating the detailed roles of miRNAs that are aberrantly expressed in cervical cancer and the underlying molecular mechanisms is essential for early diagnosis and effective therapeutic approaches. miRNA-877 (miR-877) was found to be downregulated in hepatocellular carcinoma and renal cell carcinoma, and function as a tumor-suppressive miRNA. However, how miR-877 exerts an effect in cervical cancer progression and its underlying molecular mechanisms remains to be elucidated. In the current study, reverse transcription-quantitative PCR was performed to determine miR-877 expression in cervical cancer tissues and cell lines. The effects of miR-877 overexpression on cervical cancer cell proliferation and invasion were evaluated using MTT and Transwell cell invasion assays. In the present study, miR-877 was significantly downregulated in cervical cancer tissues and cell lines, and the decreased expression levels of miR-877 were significantly associated with increased International Federation of Gynecology and Obstetric stage as well as increased lymph node metastasis in patients with cervical cancer. Upregulation of miR-877 using miR-877 mimics resulted in the decreased proliferation and invasion of cervical cancer cells. Metastasis-associated in colon cancer-1 (MACC1) was assessed using bioinformatics analyses to determine whether it could be a potential target gene of miR-877, and the results were confirmed using a luciferase reporter assay. Furthermore, MACC1 was markedly upregulated in cervical cancer tissues, and its level was negatively correlated with the miR-877 level. Overexpression of miR-877 resulted in decreased expression levels of MACC1 in cervical cancer cells at both the mRNA and protein levels. In addition, the functional effects of MACC1 knockdown were similar to those induced by upregulated miR-877 in cervical cancer cells. MACC1 restored miR-877 overexpression-mediated suppression of cervical cancer cell proliferation and invasion. In conclusion, miR-877 may play an antitumor role in cervical cancer by directly targeting MACC1, which suggests that this miRNA may be a promising therapeutic target for the treatment of patients with such an aggressive gynecological cancer.
引用
收藏
页码:3650 / 3658
页数:9
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