MicroRNA-21 regulates the sensitivity of diffuse large B-cell lymphoma cells to the CHOP chemotherapy regimen
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ORIGINAL ARTICLE
MicroRNA-21 regulates the sensitivity of diffuse large B-cell lymphoma cells to the CHOP chemotherapy regimen Haitao Bai • Ju Wei • Chong Deng • Xiaoyu Yang • Chun Wang • Rang Xu
Received: 1 July 2012 / Revised: 17 December 2012 / Accepted: 17 December 2012 / Published online: 30 December 2012 Ó The Japanese Society of Hematology 2012
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-jB decreased miR-21 expression and sensitized CRL2631 cells to CHOP H. Bai and J. Wei contributed equally to this work. H. Bai J. Wei C. Wang Department of Haematology, Shanghai Jiaotong University Affiliated Shanghai First People’s Hospital, Shanghai, China C. Deng Department of Radiation Oncology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China X. Yang Department of Cardiology, Suzhou University Affiliated Changzhou First People’s Hospital, Changzhou, Jiangsu, China R. Xu (&) Science and Research Center, Shanghai Jiaotong University Affiliated Shanghai Xinhua Hospital, No. 1665 KongJiang Road, Shanghai 200093, China e-mail: [email protected]
treatment. These results provide evidence that it may be possible to overcome microRNA-based DLBCL drug resistance. Keywords miR-21 Diffuse large B-cell lymphoma Drug resistance PTEN NF-jB
Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common histological type of non-Hodgkin lymphoma, accounting for 30–40 % of non-Hodgkin lymphoma cases in adults [1]. The combined chemotherapy represented by the cyclophosphamide, vincristine, Adriamycin, and prednisone (CHOP) regimen is the standard chemotherapeutic regimen for treating DLBCL. However, nearly half of the patients treated with the CHOP regimen stop responding to treatment and become drug resistant. Therefore, drug resistance is a major obstacle to the successful treatment of DLBCL [2, 3]. Studies have suggested that abnormalities in diverse, complicated signaling pathways, including NF-jB, CDKs, BCL-2, and P53, are involved in drug resistance [4], but the exact mechanism underlying DLBCL drug resistance is still unclear. microRNA (miRNA) includes a group of endogenous, noncoding, regulatory RNAs with lengths of approximately 20 nu
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