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首页> 外文期刊>Oncogene >Role of eIF3a in regulating cisplatin sensitivity and in translational control of nucleotide excision repair of nasopharyngeal carcinoma
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Role of eIF3a in regulating cisplatin sensitivity and in translational control of nucleotide excision repair of nasopharyngeal carcinoma

机译：eIF3a在调节顺铂敏感性和翻译控制鼻咽癌核苷酸切除修复中的作用

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Translational control at the initiation step has been recognized as a major and important regulatory mechanism of gene expression. Eukaryotic initiation factor-3a (eIF3a), a putative subunit of the eIF3 complex, has recently been shown to have an important role in regulating the translation of a subset of mRNAs and is found to correlate with the prognosis of cancers. In this study, using nasopharyngeal carcinoma (NPC) cells as a model system, we tested the hypothesis that eIF3a negatively regulates the synthesis of nucleotide excision repair (NER) proteins, and, in turn, cellular response to treatments with DNA-damaging agents such as cisplatin (cis -dichlorodiammine platinum(II) (CDDP)). We found that a CDDP-sensitive sub-clone S16 isolated through limited dilution from an NPC cell line CNE-2 has increased eIF3a expression. Knocking down its expression in S16 cells increased cellular resistance to CDDP, NER activity and synthesis of the NER proteins XPA, XPC, RAD23B and RPA32. Altering eIF3a expression also changed the cellular response to CDDP and UV treatment in other NPC cell lines. Taken together, we conclude that eIF3a has an important role in the CDDP response and in NER activity of NPCs by suppressing the synthesis of NER proteins.
机译：在起始步骤的翻译控制已被认为是基因表达的主要和重要调控机制。真核生物起始因子3a（eIF3a）是eIF3复合体的推定亚基，最近已显示出在调节mRNA子集的翻译中起重要作用，并发现与癌症的预后相关。在这项研究中，我们使用鼻咽癌（NPC）细胞作为模型系统，验证了eIF3a负调节核苷酸切除修复（NER）蛋白质的合成，进而对细胞对DNA破坏剂治疗的反应的假设。作为顺铂（顺式-二氯二氨铂（II）（CDDP））。我们发现通过从NPC细胞系CNE-2进行有限稀释而分离出的CDDP敏感亚克隆S16具有增加的eIF3a表达。降低其在S16细胞中的表达可提高细胞对CDDP的抵抗力，NER活性以及NER蛋白XPA，XPC，RAD23B和RPA32的合成。改变eIF3a表达也改变了其他NPC细胞系对CDDP和UV处理的细胞反应。两者合计，我们得出结论，eIF3a通过抑制NER蛋白的合成在CDDP反应和NPC的NER活性中具有重要作用。

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