PDF(Pubmed)
Abstract：
Neuroblastoma (NB), a common solid tumour in young children originating from the sympathetic nervous system during embryonic development, poses challenges despite therapeutic advances like high-dose chemotherapy and immunotherapy. Some survivors still grapple with severe side effects and drug resistance. The role of lncRNA NUTM2A-AS1 has been explored in various cancers, but its function in drug-resistant NB progression is unclear. Our study found that NUTM2A-AS1 expression in cisplatin-resistant NB cells increased in a time- and dose-dependent manner. Knockdown of NUTM2A-AS1 significantly improved NB cell sensitivity to cisplatin and inhibited metastatic abilities. Additionally, we identified B7-H3, an immune checkpoint-related protein, as a NUTM2A-AS1-associated protein in NB cells. NUTM2A-AS1 was shown to inhibit the protein degradation of B7-H3. Moreover, NUTM2A-AS1 modulated immune evasion in cisplatin-resistant NB cells through B7-H3. Furthermore, NUTM2A-AS1 expression in cisplatin-resistant NB cells was transactivated by NR1D1. In summary, our results unveil the molecular or biological relationship within the NR1D1/NUTM2A-AS1/B7-H3 axis in NB cells under cisplatin treatment, providing an intriguing avenue for fundamental research into cisplatin-resistant NB.
摘要：
神经母细胞瘤(NB),幼儿常见的实体瘤，起源于胚胎发育过程中的交感神经系统，尽管大剂量化疗和免疫疗法等治疗进展，但仍面临挑战。一些幸存者仍在努力应对严重的副作用和耐药性。lncRNANUTM2A-AS1在各种癌症中的作用已被探索，但其在耐药NB进展中的作用尚不清楚。我们的研究发现顺铂耐药NB细胞中NUTM2A-AS1的表达呈时间和剂量依赖性增加。NUTM2A-AS1的敲减显着提高了NB细胞对顺铂的敏感性并抑制了转移能力。此外,我们确定了B7-H3，一种免疫检查点相关蛋白，作为NB细胞中的NUTM2A-AS1相关蛋白。显示NUTM2A-AS1抑制B7-H3的蛋白质降解。此外，NUTM2A-AS1通过B7-H3调节顺铂耐药NB细胞的免疫逃避。此外，NUTM2A-AS1在顺铂抗性NB细胞中的表达被NR1D1反式激活。总之,我们的结果揭示了在顺铂处理下NB细胞NR1D1/NUTM2A-AS1/B7-H3轴内的分子或生物学关系，为顺铂耐药NB的基础研究提供了一条有趣的途径。
