Effect of miR-146 a-5 p on proliferation and metastasis of triple-negative breast cancer via regulation of SOX 5

MicroRNA (miR)-146a-5p functions as a tumor suppressor in various types of cancer. However, the role of miR-146a-5p in the development of triple-negative breast cancer (TNBC) is unclear. The present study aimed to investigate the role of miR-146a-5p in TNBC. The expression level of miR-146a-5p in TNBC tissues and cell lines was initially detected using reverse transcription-quantitative polymerase chain reaction. To predict the target gene of miR-146a-5p, TargetScan software was used and a dual luciferase assay was performed to verify the prediction. Furthermore, in order to explore the role of miR-146a-5p in TNBC, miR-146a-5p was overexpressed in TNBC cells using miR-146a-5p mimics. An MTT assay was performed to detect cell proliferation, and a Transwell assay was conducted to determine cell migration and invasion. Furthermore, western blotting was performed to measure associated protein expression. It was revealed that miR-146a-5p was downregulated in TNBC tissues and cell lines. SOX5 was indicated to be a target gene of miR-146a-5p and was upregulated in TNBC cells. Additionally, miR-146a-5p could inhibit TNBC cell proliferation, migration and invasion, repress the expression of mesenchymal markers (N-cadherin, vimentin and fibronectin) and increase epithelial marker (E-cadherin) expression. Furthermore, SOX5 overexpression eliminated the effects of miR-146a-5p mimics on TNBC cells. In conclusion, the data of the present study indicated that miR-146a-5p inhibits the proliferation and metastasis of TNBC cells by regulating SOX5. Introduction Breast cancer, which is considered to be the most common type of cancer in women worldwide (1), is divided into four sub-types, including luminal A-like, luminal B-like, human epidermal receptor-2 (HER-2) positive and triple-negative breast cancer (TNBC) (2). TNBC is characterized by the loss of expression of progesterone receptor, estrogen receptor and HER-2 gene expression (3). In total, 15-20% of breast cancer cases are TNBC and the majority of these are basal-like (4). TNBC, particularly the basal-like type, has higher rates of metastasis and poorer survival rates compared with other breast cancer sub-types (4). Previously, great improvements have been made in the early detection and treatment of breast cancer. However, due to sub‐optimal hormonal therapy and a lack of more specific and effective therapeutic targets, TNBC treatment remains a challenge (5,6). Thus, identifying biological markers of TNBC progress is necessary and could provide novel therapeutic strategies for TNBC treatment. MicroRNAs (miRs) are a class of endogenous, non-coding, single-stranded RNAs that are widely expressed in eukaryotes and are 18-22 nucleotides in length. They serve critical roles in the regulation of gene expression. Furthermore, they are involved in a series of pathological and physiological processes, including tumor proliferation, differentiation and apoptosis (7-9). Furthermore, miRs can transcriptionally inhibit the expression of target genes by binding to the 3'-untranslated region (3'-UTR), acting as oncogenes or tumor inhibitors (10). A growing number of studies have indicated that abnormal expression of miRs is associated with human breast cancer (11-16). Furthermore, mounting evidence indicates that miRs serve key functions in the development of TNBC (17-19). However, the exact molecular mechanism of miRs in TNBC is not yet understood. miR‐146a‐5p has been identified as a tumor suppressor in various types of cancer. Zhang et al (20) reported that miR-146a-5p was downregulated in hepatocellular carcinoma and acted as a tumor suppressor. Wang et al (21) revealed that miR-146a-5p promoted esophageal squamous cell carcinoma progression by regulating epithelial-mesenchymal transition (EMT) via targeting Notch2. Furthermore, miR-146a-5p has been confirmed to inhibit non‐small cell lung cancer (NSCLC) cell proliferation and cell cycle progression (22). Another study indicated that miR-146a-5p could promote prostate cancer cell Effect of miR-146a-5p on proliferation and metastasis of triple-negative breast cancer via regulation of SOX5 CHENGSHUAI SI, QIAO YU and YUFENG YAO Department of General Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research and Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu 210009, P.R. China Received July 6, 2017; Accepted October 25, 2017 DOI: 10.3892/etm.2018. 5945 Correspondence to: Dr Yufeng Yao, Department of General Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research and Nanjing Medical University Affiliated Cancer Hospital, 42 Baiziting Road, Nanjing, Jiangsu 210009, P.R. China E-mail: yaoyf2017@163.com