Department of Nutrition and Food Hygiene, Key Laboratory of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Chem Biol Interact. 2018 Dec 25;296:154-161. doi: 10.1016/j.cbi.2018.10.001. Epub 2018 Oct 3.
Long non-coding RNAs (lncRNAs) have been identified to exert crucial roles in tumorigenesis and can serve as novel biomarkers for cancer therapy including lung cancer. Cisplatin is a first-line chemotherapeutic agent in non-small cell lung cancer (NSCLC), but the therapeutic effect is unsatisfactory, partly due to drug resistance. Emerging evidence showed that chemo-resistance is associated with acquisition of cancer stem cell (CSC)-like properties. Cisplatin resistance remains a major obstacle in the treatment of lung cancer, and its mechanism is still not fully elucidated. Meanwhile, CSCs have been involved in tumor metastasis, tumor recurrence and chemotherapy resistance. So far, the mechanism of nuclear enriched abundant transcript 1 (NEAT1) in modulating CSCs in lung cancer remains barely known. Therefore, we aimed to explore the correlation between NEAT1 and cancer stem cells in lung cancer. In our current study, we observed that CSC-like traits were much more enriched in cisplatin-resistant A549/CDDP cells. In addition, NEAT1 was obviously up-regulated in A549/CDDP cells compared with parental A549 cells. Knockdown of NEAT1 decreased the CSC-like properties of A549/CDDP cells through inhibiting tumor cell sphere volume, repressing CSC-like biomarkers levels and restraining CD44 positive cell ratios. Oppositely, overexpression of NEAT1 enhanced the stemness respectively. Moreover, it has been reported that Wnt pathway is implicated in many vital cellular functions including cancer stem cells. Here, it was exhibited that Wnt signal pathway was inactivated by knockdown of NEAT1 whereas activated by NEAT1 overexpression in A549/CDDP cells. Taken these together, it was indicated that NEAT1 could exert a novel biological role in NSCLC chemo-resistance.
长链非编码 RNA（lncRNA）已被确定在肿瘤发生中发挥关键作用，并可作为癌症治疗的新型生物标志物，包括肺癌。顺铂是非小细胞肺癌（NSCLC）的一线化疗药物，但治疗效果并不理想，部分原因是耐药性。新出现的证据表明，化疗耐药性与获得癌症干细胞（CSC）样特性有关。顺铂耐药性仍然是肺癌治疗的主要障碍，其机制尚未完全阐明。同时，CSC 已参与肿瘤转移、肿瘤复发和化疗耐药。到目前为止，核丰富转录物 1（NEAT1）在调节肺癌中的 CSC 中的作用机制仍知之甚少。因此，我们旨在探讨 NEAT1 与肺癌中的 CSC 之间的相关性。在我们目前的研究中，我们观察到，在顺铂耐药的 A549/CDDP 细胞中，CSC 样特征更为丰富。此外，与亲本 A549 细胞相比，A549/CDDP 细胞中 NEAT1 明显上调。敲低 NEAT1 通过抑制肿瘤细胞球体体积、抑制 CSC 样标志物水平和抑制 CD44 阳性细胞比例，降低了 A549/CDDP 细胞的 CSC 样特性。相反，过表达 NEAT1 分别增强了干细胞特性。此外，据报道 Wnt 通路参与包括癌症干细胞在内的许多重要细胞功能。这里显示，通过敲低 NEAT1 可使 A549/CDDP 细胞中的 Wnt 信号通路失活，而过表达 NEAT1 则可激活该通路。综上所述，表明 NEAT1 可能在 NSCLC 化疗耐药中发挥新的生物学作用。
