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MicroRNA-21 regulates the sensitivity of diffuse large B-cell lymphoma cells to the CHOP chemotherapy regimen
Authors:Haitao Bai  Ju Wei  Chong Deng  Xiaoyu Yang  Chun Wang  Rang Xu
Affiliation:1. Department of Haematology, Shanghai Jiaotong University Affiliated Shanghai First People’s Hospital, Shanghai, China
2. Department of Radiation Oncology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
3. Department of Cardiology, Suzhou University Affiliated Changzhou First People’s Hospital, Changzhou, Jiangsu, China
4. Science and Research Center, Shanghai Jiaotong University Affiliated Shanghai Xinhua Hospital, No. 1665 KongJiang Road, Shanghai, 200093, China
Abstract:Numerous studies have demonstrated that microRNA-21 (miR-21), as an oncogene, is involved in the occurrence of many types of tumor and the sensitivity of tumor cells to chemotherapeutic drugs. In the present study, we investigated whether miR-21 is involved in regulating the sensitivity of the diffuse large B-cell lymphoma (DLBCL) cell line CRL2631 to the cyclophosphamide, vincristine, Adriamycin, and prednisone (CHOP) chemotherapeutic regimen. Knockdown of miR-21 with antisense oligonucleotides significantly increased the cytotoxic effects of the CHOP regimen in CRL2631 cells. A luciferase reporter assay showed that PTEN is a target gene of miR-21 in CRL2631 cells, and subsequent experiments demonstrated that miR-21 impacts the PI3K/AKT signaling pathway through the regulation of PTEN, thereby affecting cellular sensitivity to the CHOP chemotherapeutic regimen. Furthermore, knockdown of NF-κB decreased miR-21 expression and sensitized CRL2631 cells to CHOP treatment. These results provide evidence that it may be possible to overcome microRNA-based DLBCL drug resistance.
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