School of Nursing, Fujian University of Traditional Chinese Medicine, Fujian 350122, People's Republic of China.
Department of Medical Oncology, Fujian Medical University Union Hospital, Fujian 350000, People's Republic of China.
J Biochem Mol Toxicol. 2018 Jan;32(1). doi: 10.1002/jbt.22008. Epub 2017 Dec 4.
Although dexamethasone (DEX) remains a first-line agent for multiple myeloma (MM) therapy, the development of DEX resistance has become an indicator of poor prognosis in MM patients. It is thus urgent to develop strategies to restore the vulnerability of MM to DEX. This study demonstrated long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) was highly expressed in DEX-resistant myeloma cell lines, and upregulation of NEAT1 was tightly linked to poor prognosis. The in-depth study revealed that during the development of DEX resistance in these cells, the miR-193a levels were decreased, which resulted in the increased expression of the target gene myeloid cell leukemia-1 (MCL1). We also found knockdown of NEAT1, the DEX-induced sensitivity was enhanced in the resistant cells. Meanwhile, overexpression of NEAT1 increased the DEX-induced resistance in the sensitive cells. In conclusion, the NEAT1/miR-193a/MCL1 pathway is closely associated with the development of DEX resistance in myeloma cells, and knockdown of NEAT1 can significantly improve DEX sensitivity in MM.
尽管地塞米松（DEX）仍然是多发性骨髓瘤（MM）治疗的一线药物，但 DEX 耐药的发展已成为 MM 患者预后不良的指标。因此，迫切需要开发策略来恢复 MM 对 DEX 的敏感性。本研究表明，长链非编码 RNA（lncRNA）核斑蛋白组装转录本 1（NEAT1）在 DEX 耐药骨髓瘤细胞系中高表达，并且 NEAT1 的上调与不良预后密切相关。深入研究表明，在这些细胞中 DEX 耐药性发展过程中，miR-193a 水平降低，导致靶基因髓样细胞白血病-1（MCL1）的表达增加。我们还发现，敲低 NEAT1 可增强耐药细胞中 DEX 诱导的敏感性。同时，过表达 NEAT1 可增加敏感细胞中 DEX 诱导的耐药性。总之，NEAT1/miR-193a/MCL1 通路与骨髓瘤细胞中 DEX 耐药的发展密切相关，敲低 NEAT1 可显著提高 MM 中 DEX 的敏感性。
