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

Abstract

Abstract. 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.

Identification of cancer-related miRNA-lncRNA biomarkers using a basic miRNA-lncRNA network

“…Feng et al [ 58 ] reported that miR-224 down-regulates the expression of fizzled 5 to inhibit the proliferation and migration of breast cancer cells. MiR-452, as a tumor-inhibitor of breast cancer, targets the RAB11A gene directly [ 60 ].…”

Intermittent Hypoxia Up-Regulates CCL2, RETN, and TNFα mRNAs in Adipocytes via Down-regulation of miR-452

“…They affect the stability of their target mRNAs, resulting in changes in the amount of target mRNA, which is one of the mechanisms of post-transcriptional regulation. Until now, some studies about the role of miR-452 have been performed in malignant neoplasms such as pancreatic cancer [46], glioma [47], lung cancer [48,49], and breast cancer [50]. A number of studies have indicated that miRNAs play roles in the regulation of many biological processes (migration, metastasis, cell proliferation, apoptosis, chemosensitivity, etc.)…”

GPCRs in Cancer: Protease-Activated Receptors, Endocytic Adaptors and Signaling

“…Both Rab11A and Rab11B show significant changes in expression in various human cancer types with a prevalence for Rab11A ( Table 2 ). Other studies further suggest that Rab11A has an oncogenic role in several cancers including colorectal [ 69 ], pancreatic [ 70 ], breast [ 71 , 72 ], and lung cancers [ 73 ]. Rab11A overexpression promotes cellular transformation by regulating E-cadherin turnover in colorectal cancer cells [ 69 ].…”

“…In pancreatic cancer, Rab11A expression correlates with tumor-node-metastasis stage and promotes cell proliferation, cell cycle progression and invasion through GSK3β/Wnt/β-catenin pathway [ 70 ]. In breast cancer cells, downregulation of Rab11A by tumor suppressor miRNA miR-320a and miR-452 inhibits breast cancer growth, motility and invasion [ 71 , 72 ]. In lung cancer, high Rab11A levels correlate with advanced stage and poor survival [ 73 ].…”