MicroRNA-21 regulates the sensitivity of diffuse large B-cell lymphoma cells to the CHOP chemotherapy regimen

被引:95
作者
Bai, Haitao [1 ]
Wei, Ju [1 ]
Deng, Chong [2 ]
Yang, Xiaoyu [3 ]
Wang, Chun [1 ]
Xu, Rang [4 ]
机构
[1] Shanghai Jiao Tong Univ, Affiliated Shanghai Peoples Hosp 1, Dept Haematol, Shanghai 200093, Peoples R China
[2] Xiamen Univ, Affiliated Hosp 1, Dept Radiat Oncol, Xiamen, Fujian, Peoples R China
[3] Suzhou Univ, Affiliated Changzhou Peoples Hosp 1, Dept Cardiol, Changzhou, Jiangsu, Peoples R China
[4] Shanghai Jiao Tong Univ, Affiliated Shanghai Xinhua Hosp, Sci & Res Ctr, Shanghai 200093, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-21; Diffuse large B-cell lymphoma; Drug resistance; PTEN; NF-kappa B; TUMOR-SUPPRESSOR GENE; DRUG-RESISTANCE; EXPRESSION; CANCER; PATHWAY; TARGET; APOPTOSIS; SURVIVAL; INVASION; GROWTH;
D O I
10.1007/s12185-012-1256-x
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
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-kappa B 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.
引用
收藏
页码:223 / 231
页数:9
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