MiR-93 suppresses tumorigenesis and enhances chemosensitivity of breast cancer via dual targeting E2F1 and CCND1
| العنوان: | MiR-93 suppresses tumorigenesis and enhances chemosensitivity of breast cancer via dual targeting E2F1 and CCND1 |
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| المؤلفون: | Liang Xu, Weiyang Lou, Yunkun Lu, Weimin Fan, Danni Chen, Bisha Ding, Chang Bao, Jishun Chen |
| المصدر: | Cell Death and Disease, Vol 11, Iss 8, Pp 1-14 (2020) Cell Death & Disease |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Cell cycle checkpoint, Carcinogenesis, Apoptosis, medicine.disease_cause, Retinoblastoma Protein, 0302 clinical medicine, Breast cancer, E2F1, Cyclin D1, Phosphorylation, Promoter Regions, Genetic, Gene knockdown, lcsh:Cytology, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Female, biological phenomena, cell phenomena, and immunity, endocrine system, Paclitaxel, Immunology, Down-Regulation, Mice, Nude, Breast Neoplasms, Biology, Models, Biological, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cell Line, Tumor, microRNA, medicine, Animals, Humans, lcsh:QH573-671, Cell Proliferation, Cell growth, Cell Biology, Cell Cycle Checkpoints, DNA Methylation, Minichromosome Maintenance Complex Component 7, MicroRNAs, 030104 developmental biology, Drug Resistance, Neoplasm, Cancer research, Proto-Oncogene Proteins c-akt, E2F1 Transcription Factor |
| الوصف: | Chemoresistance of tumors often leads to treatment failure in clinical practice, which underscores pivotal needs to uncover novel therapeutic strategies. Accumulating evidences show that microRNAs (miRNAs) are widely involved in carcinogenesis, but their function on chemoresistance remains largely unexplored. In this study, we found that miR-93-5p (miR-93) significantly inhibited cell proliferation, induced G1/S cell cycle arrest and increased chemosensitivity to paclitaxel (PTX) in vitro and in vivo. Moreover, two well-established oncogenes, E2F1 and CCND1, were identified as dual targets of miR-93. Knockdown of E2F1 and CCND1 reduced cell proliferation and PTX-sensitivity, whereas overexpression of them had the opposite effect. More importantly, overexpression of E2F1 and CCND1 antagonized miR-93-mediated cell cycle arrest and apoptosis. Further mechanistic study revealed that miR-93 exhibited its inhibitory role by directly targeting E2F1 and CCND1 to inactivate pRB/E2F1 pathway and AKT phosphorylation. Taken together, our findings suggested that miR-93 greatly improved chemosensitivity and potentially served as a novel therapeutic target for breast cancer treatment. |
| اللغة: | English |
| تدمد: | 2041-4889 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::18de332bf7b446b210cc42302c6a8e94Test http://link.springer.com/article/10.1038/s41419-020-02855-6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....18de332bf7b446b210cc42302c6a8e94 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20414889 |
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