Tumor-suppressive microRNA-452 inhibits migration and invasion of breast cancer cells by directly targeting RAB11A

被引:26
|
作者
Li, Wanjun [1 ]
Li, Guoyin [1 ]
Fan, Zhigang [2 ]
Liu, Tao [1 ]
机构
[1] Xi An Jiao Tong Univ, Affiliated Hosp 3201, Dept Pathol, 783 Tianhan Rd, Hanzhong 723000, Shaanxi, Peoples R China
[2] Xi An Jiao Tong Univ, Affiliated Hosp 3201, Dept Med Oncol, Hanzhong 723000, Shaanxi, Peoples R China
关键词
breast cancer; microRNA-452; metastasis; RAB11A; DOWN-REGULATION; UP-REGULATION; PROLIFERATION; PROMOTES; GENE; METASTASIS; EXPRESSION; CARCINOMA;
D O I
10.3892/ol.2017.6426
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Breast cancer is the most common type of malignant tumor in females, and metastasis is the most common cause of breast cancer-associated mortality. Previous studies have identified that abnormal expression of microRNAs is commonly observed in human cancer and may be crucial for cancer metastasis. In the present study, microRNA-452 (miR-452) was investigated for its ability to act as a tumor suppressor in breast cancer. miR-452 expression was quantified in breast cancer tissue samples and cell lines with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Transwell migration and invasion assays were used to investigate the effect of miR-452 on the migration and invasion capabilities of breast cancer cells. Potential target genes of miR-452 were identified with miRanda and TargetScan. A luciferase reporter assay was performed to validate RAB11A as a putative target of miR-452, and was corroborated by RT-qPCR and western blot analyses. Finally, small interfering RNA (siRNA) was used to knockdown RAB11A expression and confirm whether miR-452 inhibited breast cancer cell migration and invasion via the negative regulation of RAB11A. The results revealed that miR-452 was downregulated in breast cancer tissues and cell lines, and that its downregulation may be associated with breast cancer metastasis, as miR-452 expression inhibited the migration and invasion capacities of breast cancer cells. RT-qPCR and western blot analyses indicated that miR-452 negatively regulated the expression of RAB11A mRNA and protein. The luciferase reporter assay revealed that miR-452 specifically bound to the 3'-untranslated region of RAB11A. Furthermore, inhibition of RAB11A with siRNA inhibited breast cancer cell migration and invasion. In conclusion, the present study has demonstrated that miR-452 may act as a tumor suppressor gene via inhibition of cell migration and invasion by targeting RAB11A in breast cancer.
引用
收藏
页码:2559 / 2565
页数:7
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