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Effect of targeting regulation of CCND1 gene-mediated FrA-1/IL-6/Stat3 signaling pathway by MiR-19a-3p on invasion and metastasis of breast cancer |
CHEN Xiuying1 and WANG Hongyuan2 |
1.Department of Mammary Glands, 2.Department of Pathology,Maternal and Child Health Hospital, Rizhao, 276800,China |
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Abstract Objective To explore the potential mechanism by which regulation of FrA-1/IL-6/Stat3 signaling pathway by miR-19a-3p targeting CCND1 genes affects the invasion and metastasis of breast cancer.Methods Tumor cells were grouped and transfected (blank group, negative control group, miR-19a-3p mimic group, miR-19a-3p inhibitor group, siRNA-CCND1 group, and miR-19a-3p mimic + siRNA-CCND1 group). Quantitative RT-PCR, Western blot, MTT, scratch test and Transwell invasion test were used to detect the expressions of related genes and proteins, as well as the changes of biological behavior of cells.Results The expressions of CCND1 and Fra-1 in human breast cancer tissues and cells increased, while the expression of miR-19a-3p decreased significantly, and there was significant difference between these groups (All P<0.05). Compared with the blank group and negative control group, the expression level of miR-19a-3p in the miR-19a-3p mimic group and siRNA-CCND1 group increased significantly, while CCND1 and Fra-1 decreased significantly, and cell proliferation, migration, invasion and metastasis decreased (All P<0.05). The expression levels of CCND 1 and Fra-1 in the miR-19a-3p inhibitor group increased, but the level of miR-19a-3p decreased, and the ability of proliferation, migration, invasion and metastasis increased significantly (All P<0.05).In addition, the above-mentioned changes were more significant in the miR-19a-3p mimic + siRNA-CCND1 group than in the miR-19a-3p mimic group and siRNA-CCND1 group, and there was significant difference between these groups (All P<0.05).Conclusions Down-regulation of miR-19a-3p is detected in breast cancer and up-regulation of miR-19a-3p can effectively contain the invasion and metastasis of breast cancer cells by inhibiting the expression of CCND1 genes and activating FrA-1/IL-6/Stat3 pathway
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Received: 10 January 2019
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