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miR-613 inhibits cell migration and invasion by downregulating Daam1 in triple-negative breast cancer
Institution:1. Department of Oncology, Traditional Chinese Medical Hospital of Siyang County, Siyang 223700, Jiangsu, China;2. Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, Nanjing 211166, Jiangsu, China;3. Department of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210009, Jiangsu, China;4. Department of Oncology, Zhongda Hospital Southeast University, Nanjing 210009, Jiangsu, China;5. Department of Radiotherapy, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, Jiangsu, China;6. Department of Chemotherapy, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210009, Jiangsu, China;7. Department of Physiology, Nanjing Medical University, Nanjing 211166, Jiangsu, China;8. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, Jiangsu, China;1. Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, United States;2. Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI, United States;1. Department of General Surgery, Cao County People''s Hospital, Heze, Shandong Province 274400, China;2. Department of Biliary Tract Surgery, Third Affiliated Hospital of Second Military Medical University, Shanghai 200438, China;3. Department of General Surgery, First Affiliated Hospital of Second Military Medical University, Shanghai, 200433, China;4. Department of Oncology, Cao County People''s Hospital, Heze, Shandong Province 274400, China;1. Department of Molecular Biology, Netaji Subhas Chandra Bose Cancer Research Institute, 3081 Nayabad, Kolkata 700094, India;2. Cancer Biology and Inflammatory Disorder Division, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700032, India;3. Department of Biological Sciences, BITS Pilani, K K Birla Goa Campus, India;4. Department of Pathology, Netaji Subhas Chandra Bose Cancer Research Institute, 3081 Nayabad, Kolkata 700094, India;5. Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, Shyamaprasad Mukherjee Rd, Kolkata, West Bengal 700026, India;6. Department of Haematooncology, Netaji Subhas Chandra Bose Cancer Research Institute, 3081 Nayabad, Kolkata 700094, India
Abstract:Dishevelled-associated activator of morphogenesis 1 (Daam1) is a formin protein and participates in regulating cell migration of triple-negative breast cancer (TNBC) cells. The specific miRNA targeting Daam1 and mediating cell migration and invasion remains obscure. This experiment investigated the suppressive role of miR-613 in TNBC cells. The luciferase activity of Daam1 3′-untranslated region (3′-UTR) based reporters constructed in HEK-293T and MCF-7 cells suggested that Daam1 was the target gene of miR-613. Overexpressed miR-613 reduced the protein level of Daam1, weakened RhoA activity, and retarded the cell migration, cell invasion and colony formation of TNBC cells. Overexpression of Daam1 or RhoA rescued cell migration and invasion in miR-613-overexpressed TNBC cells, but failed to reverse colony formation. MiR-613 was significantly downregulated in breast cancer tissues compared with that in adjacent normal tissues. This downregulation in TNBC tissues and lymphnode metastatic breast cancer tissues was more obvious than that in non-TNBC tissues and non-metastatic cancer tissues, respectively. MiR-613 weakens the resistance of TNBC cells against paclitaxel rather than adriamycin, cyclophosphamide, docetaxel, and kaempferol. Taken together, miR-613 is involved in cell migration and invasion of TNBC cells via targeting Daam1/RhoA signaling pathway.
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