Downregulation of miR-221 enhances the sensitivity of human oral squamous cell carcinoma cells to Adriamycin through upregulation of TIMP3 expression |
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| Institution: | 1. Department of Oral & Maxillofacial Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China;2. Department of Oral & Maxillofacial Surgery, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China;3. Department of Stomatology, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, China;4. Department of oral and maxillofacial surgery of Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China;1. Senior Resident, Department of Oral and Maxillofacial Surgery, Mount Sinai St Luke''s-Roosevelt Hospital, New York, NY;2. Former Chief Resident, Department of Oral and Maxillofacial Surgery, Mount Sinai St Luke''s-Roosevelt Hospital, New York, NY;3. Program Director, Department of Oral and Maxillofacial Surgery, Mount Sinai St Luke''s-Roosevelt Hospital, New York, NY;4. Site Chair, Institute for Neurology and Neurosurgery, Department of Interventional Neuroradiology, Mount Sinai St Luke''s-Roosevelt Hospital, New York, NY;1. Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich-Heine University Dusseldorf, Medical Faculty, Dusseldorf, Germany;2. Institute of Transplantation Diagnostics and Cell Therapeutics (ITZ), Heinrich-Heine University Dusseldorf, Medical Faculty, Dusseldorf, Germany;3. Centro de Biología Molecular Severo Ochoa, CSIC/Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain;4. Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Campus M. de Unamuno s/n, Salamanca, Spain;5. Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain;1. Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan;2. Department of Applied Chemistry, Kyushu Institute of Technology, Kokurakita-ku, Kitakyushu, Fukuoka 804-8550, Japan;3. Department of Oral and Maxillofacial Surgery, National Hospital Organization Kumamoto Medical Center, Chuo-ku, Kumamoto 860-0008, Japan |
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| Abstract: | Aberrantly expressed microRNAs (miRNAs) are involved in oral tumorigenesis since they can alter the expression of proteins involved in cancer progression. It remains unclear whether miRNA-221 influences the resistance of human oral squamous cell carcinoma cells to Adriamycin. We therefore investigated the role of miR-221 in the sensitivity of oral squamous cell carcinoma cells to chemotherapy. Tca8113 and UM2 cells were treated with different concentrations of Adriamycin. Quantitative real-time PCR (qRT-PCR) revealed miR-221 upregulation after Adriamycin treatment of Tca8113 and UM2 cells. By using miR-221 inhibitor mimics, we found that depleting cells of miR-221 increases the sensitivity of the cells to Adriamycin. The expression of tissue inhibitor of metalloproteinase-3 (TIMP3), a target of miR-221, was decreased in cells treated with Adriamycin. TIMP3 depletion reversed the effect of a miR-221 inhibitor mimics on cell survival rates and apoptosis. Together, these results reveal that silencing of miR-221 enhances the sensitivity of human oral squamous cell carcinoma cells to Adriamycin through upregulation of TIMP3 expression. |
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| Keywords: | miR-221 Oral squamous cell carcinoma Adriamycin TIMP3 |
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