首页> 外文期刊>Journal of biochemical and molecular toxicology >LncRNA NEAT1 promotes dexamethasone resistance in multiple myeloma by targeting miR‐193a/MCL1 pathway
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LncRNA NEAT1 promotes dexamethasone resistance in multiple myeloma by targeting miR‐193a/MCL1 pathway

机译:通过靶向miR-193a / mcl1途径,LNCRNA Neat1促进多发性骨髓瘤的抗性抗性

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Abstract 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.
机译:摘要虽然地塞米松(DEX)仍然是多骨瘤(MM)治疗的一线剂,但抗毒性的发展已成为MM患者预后不良的指标。因此,迫切需要开发策略,以恢复mm到德克斯的脆弱性。本研究证明了长期非编码RNA(LNCRNA)核ParaSPECHLE组装转录物1(NEAT1)在耐毒性骨髓瘤细胞系中高度表达,并且NEAT1的上调与预后差有差。深入研究表明,在这些细胞的抗毒性抗性的发展期间,MIR-193A水平降低,导致靶基因骨髓细胞白血病-1(MCL1)的表达增加。我们还发现Neat1的敲低,在抗性细胞中增强了DEX诱导的敏感性。同时,Neat1的过度表达增加了敏感细胞中的抗曲率抗性。总之,Neat1 / miR-193a / mcl1途径与骨髓瘤细胞中耐毒性抗性的发育密切相关,并且Neat1的敲低可以显着提高MM的DEX敏感性。

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