Zheng Tianliang, Li Deping, He Zhanfeng, Feng Shuaibing, Zhao Song
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan Province, China.
Department of Acupuncture and Moxibustion, Zhengzhou Hospital of Traditional Chinese Medicine Zhengzhou 450000, Henan Province, China.
Am J Cancer Res. 2018 Sep 1;8(9):1801-1811. eCollection 2018.
Autophagy is critical for the survival of cancer cells. It has been reported that long noncoding RNA (lncRNA) neuroblastoma associated transcript 1 (NBAT1) exerts as a tumor suppressor in some cancers. However, the role of NBAT1 in autophagy of non-small cell lung cancer (NSCLC) remains unknown. Here, it was reported that NBAT1 overexpression inhibited autophagy, while knockdown of NBAT1 induced autophagy in NSCLC cells. Further mechanistic study showed that NBAT1 interacted with PSMD10 and promoted its degradation, and then inhibited the occupancy of PSMD10 and HSF1 in the ATG7 promoter to suppress ATG7 transcription. A significantly negative correlation between NBAT1 and ATG7 levels was observed in NSCLC tissue. The prognoses of NSCLC patients with low expression of NBAT1 were much worse than those with high-level NBAT1. Moreover, NBAT1 negatively regulated cell viability, clonogenicity, and chemoresistance through inhibition of autophagy. Our findings suggest that the NBAT1-PSMD10-ATG7 axis may be an attractive strategy in NSCLC treatment by suppressing autophagy and chemoresistance.
自噬对癌细胞的存活至关重要。据报道，长链非编码RNA（lncRNA）神经母细胞瘤相关转录本1（NBAT1）在某些癌症中发挥肿瘤抑制作用。然而，NBAT1在非小细胞肺癌（NSCLC）自噬中的作用仍不清楚。在此，有报道称NBAT1过表达抑制自噬，而敲低NBAT1则诱导NSCLC细胞自噬。进一步的机制研究表明，NBAT1与PSMD10相互作用并促进其降解，进而抑制PSMD10与HSF1在ATG7启动子上的结合以抑制ATG7转录。在NSCLC组织中观察到NBAT1与ATG7水平呈显著负相关。NBAT1低表达的NSCLC患者的预后比NBAT1高表达的患者差得多。此外，NBAT1通过抑制自噬负向调节细胞活力、克隆形成能力和化疗耐药性。我们的研究结果表明，NBAT1-PSMD10-ATG7轴可能是通过抑制自噬和化疗耐药性来治疗NSCLC的一个有吸引力的策略。
