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

• Published in: Oncology letters 2017-08, Vol.14 (2), p.2559-2565
• Main Authors: Li, Wanjun, Li, Guoyin, Fan, Zhigang, Liu, Tao
• Format: Article
• Language: English
• Subjects: Apoptosis; Breast cancer; Care and treatment; Cell adhesion & migration; Cell cycle; Chemotherapy; Cyclin-dependent kinases; Development and progression; Gene expression; Genetic aspects; Health aspects; Kinases; Liver cancer; Metastasis; MicroRNA; microRNA-452; Mortality; Oncology; Proteins; RAB11A; Surgery; Tumor suppressor genes
• ISSN: 1792-1074; 1792-1082
• DOI: 10.3892/ol.2017.6426

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.