Department of Respiratory and Critical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
Department of Respiratory and Critical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Clin Sci (Lond). 2019 Jan 30;133(2):381-392. doi: 10.1042/CS20180983. Print 2019 Jan 31.
Long non-coding RNAs (lncRNAs) have been reported to play a vital role in non-small-cell lung cancer (NSCLC). ZEB1-AS1 overexpression predicts a poor prognosis in osteosarcoma and colorectal cancers. In the current study, we determined the clinical significance and prognostic value of ZEB1-AS1 in patients with NSCLC. The expression of ZEB1-AS1 and inhibitor of differentiation-1 (ID1) was measured using qRT-PCR and Western blot. Cell growth, migration, and invasion were determined using colony formation assays, Transwell assay, and flow cytometry, respectively. Tumor growth was determined with a xenograft model. ZEB1-AS1 was significantly up-regulated in NSCLC tissues compared with normal samples. ZEB1-AS1 overexpression was significantly associated with advanced tumor, lymph node, and metastases (TNM) stage and tumor size, as well as poorer overall survival. Moreover, ZEB1-AS1 knockdown inhibited NSCLC cell proliferation and migration, and promoted cell apoptosis. In addition, a chromatin immunoprecipitation assay revealed that ZEB1-AS1 interacted with STAT3, thereby repressing ID1 expression. Furthermore, rescue experiments indicated that ZEB1-AS1 functioned as an oncogene partly by repressing ID1 in NSCLC cells. Taken together, our findings indicate that ZEB1-AS1 serves as a promising therapeutic target to predict the prognosis of NSCLC.
长链非编码 RNA（lncRNA）已被报道在非小细胞肺癌（NSCLC）中发挥重要作用。ZEB1-AS1 的过表达预测骨肉瘤和结直肠癌的预后不良。在本研究中，我们确定了 ZEB1-AS1 在 NSCLC 患者中的临床意义和预后价值。使用 qRT-PCR 和 Western blot 测量 ZEB1-AS1 和分化抑制因子-1（ID1）的表达。通过集落形成试验、Transwell 试验和流式细胞术分别测定细胞生长、迁移和侵袭。通过异种移植模型测定肿瘤生长。与正常样本相比，NSCLC 组织中 ZEB1-AS1 明显上调。ZEB1-AS1 的过表达与晚期肿瘤、淋巴结和转移（TNM）分期以及肿瘤大小显著相关，并且总生存率较差。此外，ZEB1-AS1 敲低抑制 NSCLC 细胞增殖和迁移，并促进细胞凋亡。此外，染色质免疫沉淀试验表明 ZEB1-AS1 与 STAT3 相互作用，从而抑制 ID1 的表达。此外，挽救实验表明，ZEB1-AS1 在 NSCLC 细胞中部分通过抑制 ID1 发挥致癌基因的作用。总之，我们的研究结果表明，ZEB1-AS1 可作为预测 NSCLC 预后的有前途的治疗靶点。
