Department of Pharmacy, Affiliated Xiaolan Hospital of Southern Medical University, Zhongshan, China.
Department of Oncology, Affiliated Xiaolan Hospital of Southern Medical University, Zhongshan, China.
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。
