NR1D1‐transactivated lncRNA NUTM2A‐AS1 promotes chemoresistance and immune evasion in neuroblastoma via inhibiting B7‐H3 degradation

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.