MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

Abstract

Abstract. MicroRNA (miRNA) is a type of endogenous non-coding RNA implicated in various cellular processes. Studies have shown that miR-124 is involved in the malignant progression of cancer, but little is known concerning its potential role in breast cancer. Therefore, the purpose of this study was to conduct a functional analysis of miR-124 in breast cancer, and to identify its target genes in this disease. To this end, we used quantitative real-time PCR to examine the expression level of miR-124 in breast cancer tissue specimens and cell lines. To study the functional significance of miR-124, we overexpressed miR-124 with miR-124 mimics and observed breast cancer cell proliferation, colony formation, migration, and invasion abilities by in vitro cell culture experiments. Target prediction algorithms and luciferase reporter gene assays were used to identify the target genes of miR-124. We also knocked down miR-124 targets using short hairpin RNA (shRNA) constructs, and observed associated breast cancer cell characteristics by in vitro cell culture experiments. We found that miR-124 expression significantly decreased in breast cancer tissues and cells compared to normal tissues and cells. In addition, cell proliferation, colony formation, migration, and invasion were decreased after overexpression of miR-124 in breast cancer cells. Furthermore, we used several algorithms to identify the snail family zinc finger 2 (SNAI2) as a potential target gene of miR-124. The protein expression level and luciferase activity of the 3'-untranslated region of SNAI2 were significantly decreased in breast cancer cells transfected with miR-124 mimics. Cell proliferation, colony formation, migration, and invasion were also decreased after knockdown of SNAI2 by shRNA. In conclusion, our data suggest that miR-124 expression is decreased in breast cancer and plays an important role as a tumor suppressor gene by targeting SNAI2. These findings may reveal novel perspectives for clinical treatments against breast cancer.

miR-33a-5p inhibits the growth and metastasis of melanoma cells by targeting SNAI2

“…SNAI2 was a member of SNAIL family of EMT associated transcription factors and accepted as an oncogene. Abnormally high expression of SNAI2 has been found in various cancers, including breast cancer [30], colorectal cancer [31] and melanoma [32]. Interestingly, Zhao et al first discovered that SNAI2 could as a tumor suppressor by repressing multidrug resistance via decreasing ABC transporter genes in hepatocellular carcinoma cells [33].…”

MicroRNA124 and microRNA21-5p regulate migration, proliferation and differentiation of rat bone marrow mesenchymal stem cells

“…Cell migration is an important determinant of the efficiency of MSC transplant therapy [ 41 ]. Previously, there are study reported that overexpression of miR124 suppresses the migration of several cell lineages, including glioma [ 42–44 ], bladder cancer cells [ 45 , 46 ], osteosarcoma cells [ 47 , 48 ], breast cancer cells [ 49 , 50 ], and lung cancer cells [ 51 ]. It is also reported that miR124 down-regulates Wnt/β-catenin signaling via targeting the frizzled-4 (FZD4) and low-density lipoprotein receptor-related protein 6 (LRP6) and thus suppresses the chemotactic migration of MSCs toward hepatocyte growth factor (HGF), a chemoattractant factor [ 52 ].…”

Interplay among SNAIL Transcription Factor, MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Regulation of Tumor Growth and Metastasis

“…Among them are miR-30a [70], miR-122 [95], miR-182 [115], and miR-203 [115] and miR-204 [116]. SLUG is targeted in in oral squamous cell carcinoma by miR-204 [116]; glioblastoma by miR-203 [117]; in lung cancer by miR-1 [118]; in breast cancer by miR-124 [119,120], miR-30a [70], miR-497 [121], miR-1271 [122], and miR-203 [123,124]; in gastric cancer by miR-33a [125]; in lung cancer by miR-218 [126]; in clear cell renal cell carcinoma by miR-1 [127]; in osteosarcoma by miR-124 [128]; and in gingival fibroblasts by miR-200b [129]. Similarly to SNAIL, miRNAs-SLUG action regulates EMT in cancer progression, as well as different processes, such as the modulation of cancer stem cells' activity.…”

“…Cancer/Cell Type References miR-1 lung cancer [118] miR-30a breast cancer [70] miR-33a gastric cancer [125] miR-124 breast cancer [119,120] osteosarcoma [128] glioma [130] miR-200b gingival fibroblasts [129] miR-203 glioblastoma [117] breast cancer [123,124] miR-204 oral squamous cell carcinoma [116] miR-218 lung cancer [126] miR-497 breast cancer [121] miR-630 dermal microvascular endothelial cells [131] miR-1271 breast cancer [122]…”