MicroRNA-21 regulates the sensitivity of diffuse large B-cell lymphoma cells to the CHOP chemotherapy regimen
MicroRNA-21 regulates the sensitivity of diffuse large B-cell lymphoma cells to the CHOP chemotherapy regimen
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DOI：
10.1007/s12185-012-1256-x
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发表时间：
2013-02-01
影响因子：
2.1
通讯作者：
Xu, Rang
中科院分区：
文献类型：
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作者：
Bai, Haitao;Wei, Ju;Xu, Rang
大量研究表明，microRNA-21 （miR-21）作为一种致癌基因，参与了多种肿瘤的发生以及肿瘤细胞对化疗药物的敏感性。在本研究中，我们研究了miR-21是否参与调节弥漫性大b细胞淋巴瘤（DLBCL）细胞系CRL2631对环磷酰胺、长春新碱、阿霉素和泼尼松（CHOP）化疗方案的敏感性。反义寡核苷酸敲低miR-21显著增加CHOP方案在CRL2631细胞中的细胞毒性作用。荧光素酶报告基因实验显示，在CRL2631细胞中，PTEN是miR-21的靶基因，随后的实验表明，miR-21通过调控PTEN影响PI3K/AKT信号通路，从而影响细胞对CHOP化疗方案的敏感性。此外，NF-kappa B的敲低降低了miR-21的表达，使CRL2631细胞对CHOP处理敏感。这些结果为克服基于microrna的DLBCL耐药提供了证据。
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.