NORAD 通过靶向 miR-129-1-3p/SOX4 轴加速非小细胞肺癌的化疗耐药性。
NORAD accelerates chemo-resistance of non-small-cell lung cancer via targeting at miR-129-1-3p/SOX4 axis.
机构信息
Department of Pharmacy, Affiliated Xiaolan Hospital of Southern Medical University, Zhongshan, China.
Department of Oncology, Affiliated Xiaolan Hospital of Southern Medical University, Zhongshan, China.
出版信息
Biosci Rep. 2020 Jan 31;40(1). doi: 10.1042/BSR20193489.
Substantial researches indicated that long non-coding RNAs (lncRNAs) exerted profound effects on chemo-resistance in cancer treatment. Nonetheless, the role of NORAD in non-small-cell lung cancer (NSCLC) remains unclear. In the present study, we chose NSCLC cell lines H446 and A549 to explore the function of non-coding RNA activated damage (NORAD) in response to cisplatin (DDP) resistance of NSCLC. Experimental data manifested that NORAD was up-regulated in DDP-resistant NSCLC tissues and cells. NSCLC patients with high NORAD expression suffered a poor prognosis. NORAD knockdown resensitized H446/DDP and A549/DDP to DDP. Besides, NORAD acted as a molecular sponge of miR-129-1-3p. MiR-129-1-3p showed a low level of expression in DDP-resistant NSCLC tissues. Moreover, miR-129-1-3p overexpression impaired DDP resistance in H446/DDP and A549/DDP cells. SOX4 was the downstream target of miR-129-1-3p. Especially, SOX4 overexpression offset the effects of NORAD silence on H446/DDP and A549/DDP cells resistance to DDP. NORAD knockdown resensitized H446/DDP and A549/DDP to DDP in NSCLC via targeting miR-129-1-3p/SOX4 axis, offering a brand-new target for NSCLC chemo-resistance.
大量研究表明，长非编码 RNA（lncRNAs）对癌症治疗中的化疗耐药性有深远影响。然而，NORAD 在非小细胞肺癌（NSCLC）中的作用尚不清楚。在本研究中，我们选择 NSCLC 细胞系 H446 和 A549 来探索非编码 RNA 激活损伤（NORAD）在 NSCLC 对顺铂（DDP）耐药中的作用。实验数据表明，NORAD 在 DDP 耐药的 NSCLC 组织和细胞中上调。NORAD 高表达的 NSCLC 患者预后不良。NORAD 敲低可使 H446/DDP 和 A549/DDP 对 DDP 重新敏感。此外，NORAD 作为 miR-129-1-3p 的分子海绵发挥作用。miR-129-1-3p 在 DDP 耐药的 NSCLC 组织中表达水平较低。此外，miR-129-1-3p 过表达可损害 H446/DDP 和 A549/DDP 细胞对 DDP 的耐药性。SOX4 是 miR-129-1-3p 的下游靶标。特别是，SOX4 过表达抵消了 NORAD 沉默对 H446/DDP 和 A549/DDP 细胞对 DDP 耐药性的影响。通过靶向 miR-129-1-3p/SOX4 轴，NORAD 敲低可使 NSCLC 中的 H446/DDP 和 A549/DDP 对 DDP 重新敏感，为 NSCLC 化疗耐药提供了一个全新的靶点。
Zotero 插件