Jinyan Wang1,2, Jinqiu Wang3, Quan Gu4, Yan Yang1, Yajun Ma1, Jing Zhu1, Quanan Zhang1. 1. Department of Oncology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, China. 2. Department of Oncology, The Affiliated Jiangning Hospital of Jiangsu Health Vocational College, Nanjing 211100, China. 3. Department of Oncology, Dafeng People's Hospital, Yancheng 224199, China. 4. Nanjing Medical University, Nanjing 211166, China.
Abstract
OBJECTIVE: To investigate the effect of miR-4443 expression on migration and invasion of breast cancer. METHODS: We examined the expression of miR-4443 in breast carcinoma in situ and paired adjacent tissues from 3 breast cancer patients with high-throughput sequencing and verified the results using TCGA database. We also detected miR-4443 expressions using real-time quantitative PCR (RT-qPCR) in low invasive and highly invasive breast cancer cells (MCF-7 and MDA-MB-231 cells, respectively). The changes in apoptosis, migration and invasion of MCF-7 and MDA-MB-231 cells after transfection with miR-4443 mimics, mimics-NC, miR-4443 inhibitor or inhibitor-NC were analyzed using flow cytometry, wound healing assay and Transwell invasion assay. The target gene of miR-4443 was predicted by bioinformatics software and validated by a dual luciferase reporter gene system. RT-qPCR and Western blotting were performed to detect the expression of recombinant human phosphatidyl ethanolamine binding protein 1 (PEBP1) in the transfected cells. RESULTS: The expression of miR-4443 was significantly higher in the breast cancer tissues than in the adjacent tissues (P < 0.01), and was significantly up-regulated in MDA-MB-231 cells as compared with MCF-7 cells (P < 0.01). Transfection with miR-4443 mimics or inhibitors did not obviously affect apoptosis rate of the breast cancer cells (P>0.05), but significantly enhanced or weakened the migration and invasion abilities of the cells, respectively (P < 0.01). Bioinformatic analysis identified PEBP1 as the target gene of miR-4443 with a close correlation with metastasis of breast cancer (P < 0.01), and the result was confirmed by double luciferase reporter gene assay. The mRNA and protein expression of PEBP1 were significantly lower in MDA-MB-231 cells than in MCF-7 cells (P < 0.01), and miR-4443 over-expression or knockdown significantly down-regulated or up-regulated PEBP1 expressions in the cells, respectively (P < 0.01). CONCLUSIONS: MiR-4443 promotes the migration and invasion of breast cancer cells by inhibiting the expression of PEBP1, suggesting the possibility of suppressing miR-4443 expression as a potential therapeutic strategy for breast cancer.
OBJECTIVE: To investigate the effect of miR-4443 expression on migration and invasion of breast cancer. METHODS: We examined the expression of miR-4443 in breast carcinoma in situ and paired adjacent tissues from 3 breast cancer patients with high-throughput sequencing and verified the results using TCGA database. We also detected miR-4443 expressions using real-time quantitative PCR (RT-qPCR) in low invasive and highly invasive breast cancer cells (MCF-7 and MDA-MB-231 cells, respectively). The changes in apoptosis, migration and invasion of MCF-7 and MDA-MB-231 cells after transfection with miR-4443 mimics, mimics-NC, miR-4443 inhibitor or inhibitor-NC were analyzed using flow cytometry, wound healing assay and Transwell invasion assay. The target gene of miR-4443 was predicted by bioinformatics software and validated by a dual luciferase reporter gene system. RT-qPCR and Western blotting were performed to detect the expression of recombinant human phosphatidyl ethanolamine binding protein 1 (PEBP1) in the transfected cells. RESULTS: The expression of miR-4443 was significantly higher in the breast cancer tissues than in the adjacent tissues (P < 0.01), and was significantly up-regulated in MDA-MB-231 cells as compared with MCF-7 cells (P < 0.01). Transfection with miR-4443 mimics or inhibitors did not obviously affect apoptosis rate of the breast cancer cells (P>0.05), but significantly enhanced or weakened the migration and invasion abilities of the cells, respectively (P < 0.01). Bioinformatic analysis identified PEBP1 as the target gene of miR-4443 with a close correlation with metastasis of breast cancer (P < 0.01), and the result was confirmed by double luciferase reporter gene assay. The mRNA and protein expression of PEBP1 were significantly lower in MDA-MB-231 cells than in MCF-7 cells (P < 0.01), and miR-4443 over-expression or knockdown significantly down-regulated or up-regulated PEBP1 expressions in the cells, respectively (P < 0.01). CONCLUSIONS: MiR-4443 promotes the migration and invasion of breast cancer cells by inhibiting the expression of PEBP1, suggesting the possibility of suppressing miR-4443 expression as a potential therapeutic strategy for breast cancer.
Entities:
Keywords:
breast neoplasms; microRNAs; neoplasm metastasis; phosphatidylethanolamine binding protein 1
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