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pmid:32328182
MiR-891a-5p as a prognostic marker and therapeutic target for hormone receptor-positive breast cancer.
Zhiqiang Zhang · Lu Xu · Lijie He · Jin Wang · Xiaonan Shi · Zhi Li · Sha Shi · Kezuo Hou · Yuee Teng · Xiujuan Qu
Journal of Cancer · 2020 doi:10.7150/jca.40750
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Therefore, seeking the novel biomarkers and therapeutic targets that contribute to postoperative recurrence and metastasis in patients with breast cancer is emerging and facilitates the development of innovative therapeutics. Methods: Retrieving the dataset of patients with hormone receptor (HR)-positive breast cancers from Gene Expression Omnibus (GEO) and collecting the data from the patients with HR-positive breast cancers enrolled in the First Affiliated Hospital of China Medical University are so as to identify the miRNAs associated with metastasis and distant metastasis-free survival (DMFS). Then MTT and Transwell migration assays were used to validate the effect of miRNAs on cell proliferation and migration of estrogen receptor-positive breast cancer T47D and MCF7 cells in vitro, respectively. Results: From GSE59829 dataset, the miRNA expression levels of miR-891a-5p, miR-383-5p and miR-1295a were significantly downregulated while the levels of miR-128-3p, miR-661 and miR-296-3p were significantly upregulated in breast cancers from patients with metastasis as compared to the matched non-metastatic group. Moreover, low expression levels of miR-891a-5p, miR-383-5p and miR-1295a or high expression levels of miR-128-3p, miR-661 and miR-296-3p were respectively associated with low DMFS in patients with breast cancer. Our clinical cohort study supported that the levels of miR-891a-5p, miR-383-5p and miR-1295a were significantly lower in breast cancers from the metastasis group when compared with non-metastatic group. However, there is no significant difference with regard to the levels of miR-128-3p, miR-661 and miR-296-3p in breast cancer between these two groups. Moreover, low expression levels of miR-891a-5p and miR-383-5p but not miR-1295a in breast cancer were significantly associated with low DMFS in patients, implying that the expression of miR-891a-5p and miR-383-5p were the potential prognosis markers for metastatic human breast cancers. Further investigation disclosed that miR-891a-5p but not miR-383-5p restrained both proliferation and migration of T47D and MCF7 cells. In silico analysis of miRNAs target gene through online computational algorithms revealed that A Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is the downstream target for miR-891a-5p. Further study confirmed that miR-891a-5p impeded ADAM10 expression by directly binding to its 3'UTR, leading to the inhibition of breast cancer cells proliferation and migration. Moreover, silencing ADAM10 inhibited T47D and MCF7 cells growth and migration. Conclusion: miR-891a-5p is the vital prognostic marker for HR-positive breast cancer. In addition, miR-891a-5p and miR-383-5p are the potential targets for HR-positive breast cancer therapeutics.", "claims": [{"id": "claim-method", "statement": "T-test was used for comparison between test groups and P < 0.05 was considered as statistical significance.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32328182", "locator": "sections[15] \"Statistics\" paragraph 2", "quote": "T-test was used for comparison between test groups and P < 0.05 was considered as statistical significance."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original data were retrieved from the GEO database of NCBI (www.ncbi.nlm.nih.gov/geo), and the access number is GSE59829. A total of 1146 miRNAs were detected on the platform (>97%, includes all of the miRNAs in microBase 12.0), and the access number was GPL8179. Consequently, the data from 54 cases of patients with T1N0M0, ESR1(+)/ERBB2(-) breast cancer were used in this study. 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