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Effect of nucleolin on adriamycin resistance via the regulation of B-cell lymphoma 2 expression in Burkitt's lymphoma cells |
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| Authors: | Xuqiao Mei Yanxin Chen Donghui Gan Yingyu Chen Lingyan Wang Yanqin Cao Zhengjun Wu Weijuan Liu Chenxing Zhao Minhui Lin Ting Yang Jianda Hu |
| Affiliation: | 1. Fujian Provincial Key Laboratory of Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China Department of Clinical Laboratory, The Affiliated Zhangzhou Municipal Hospital, Fujian Medical University, Zhangzhou, Fujian, China Xuqiao Mei, Yanxin Chen, and Donghui Gan contributed equally to the study.;2. Fujian Provincial Key Laboratory of Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China Xuqiao Mei, Yanxin Chen, and Donghui Gan contributed equally to the study.;3. Fujian Provincial Key Laboratory of Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China Department of Hematology, The Affiliated Hospital of Putian University, Putian, Fujian, China Xuqiao Mei, Yanxin Chen, and Donghui Gan contributed equally to the study.;4. Fujian Provincial Key Laboratory of Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China |
| Abstract: | Nucleolin (NCL, C23) is an important nucleocytoplasmic multifunctional protein. Due to its multifaceted profile and high expression in cancer, NCL is considered to be a marker of drug resistance associated with chemotherapy. However, the biochemical mechanisms in which NCL suppresses drug sensitivity in several cancers have yet to be fully elucidated. This study aims to explore the effect of NCL on drug sensitivity and its potential mechanism in CA46 Burkitt's lymphoma (BL) cells. CA46 BL cells were transfected with lentiviruses carrying the NCL gene (CA46-NCL-overexpression, CA46-NCL-OE), or shRNA sequences that target the endogenous NCL gene (CA46-NCL-knockdown, CA46-NCL-KD). Adriamycin (ADM) IC50 levels for CA46-NCL-overexpressed (OE), CA46-NCL-OE control (OEC), CA46-NCL-knockdown (KD), and CA46-NCL-KD control (KDC) cells were 0.68 ± 0.06 μg/ml, 0.68 ± 0.06 μg/ml, 0.68 ± 0.06 μg/ml, and 0.30 ± 0.04 μg/ml, respectively. Apoptosis rates were significantly increased following NCL KD, whereas the opposite effect was noted in OE cells. A significant reduction of B-cell lymphoma 2 (Bcl-2) mRNA and protein levels in KD cells was observed, while OE cells displayed the opposite effect. The stability of Bcl-2 mRNA was influenced by NCL levels, the half-life of which was extended after NCL-OE, whereas it was reduced in KD cells. Finally, results of RNA-immunoprecipitation assays indicated that NCL could bind to Bcl-2 mRNA in CA46 cells. Taken together, these results suggested that NCL could mediate Bcl-2 expression and stability, and thus enhance ADM resistance in CA46 BL cells. |
| Keywords: | adriamycin resistance Bcl-2 Burkitt's lymphoma CA46 nucleolin |