Zhang Xiaodong, Gong Jun, Lu Junguo, Chen Jia, Zhou Yan, Li Tao, Ding Lingchi
Department of Medical Oncology, Nantong Tumor Hospital Nantong 226006, Jiangsu Province, China.
Am J Transl Res. 2019 Sep 15;11(9):6075-6083. eCollection 2019.
Accumulating evidence reveals the essential roles of long noncoding RNAs (lncRNAs) in the non-small-cell lung cancer (NSCLC) tumorigenesis. Here, our research investigated the biological roles of novel lncRNA LINC00337 in the NSCLC tumorigenesis and discover the potential mechanism. In the NSCLC tissue and cell lines, LINC00337 was found to be remarkedly up-regulated, and the ectopic LINC00337 overexpression indicated the poor survival of NSCLC patients. In vitro, gain and loss of functional assays showed that LINC00337 promoted the progression of NSCLC cells, including proliferation and invasion. In vivo, LINC00337 knockdown inhibited the tumor growth of NSCLC cells. Mechanically, LINC00337 could recruit the epigenetic repressor DNMT1 to the promoter region of TIMP2 to silence its expression. In conclusion, our study found the critical regulation of lncRNA LINC00337 for the NSCLC through epigenetic regulation, which may serve as a predictive biomarker and potential therapeutic target.
越来越多的证据揭示了长链非编码RNA（lncRNAs）在非小细胞肺癌（NSCLC）肿瘤发生中的重要作用。在此，我们的研究调查了新型lncRNA LINC00337在NSCLC肿瘤发生中的生物学作用，并发现了潜在机制。在NSCLC组织和细胞系中，发现LINC00337显著上调，异位LINC00337过表达表明NSCLC患者预后不良。在体外，功能获得和缺失实验表明LINC00337促进NSCLC细胞的进展，包括增殖和侵袭。在体内，LINC00337敲低抑制了NSCLC细胞的肿瘤生长。机制上，LINC00337可将表观遗传抑制因子DNMT1募集到TIMP2的启动子区域以沉默其表达。总之，我们的研究发现lncRNA LINC00337通过表观遗传调控对NSCLC具有关键调节作用，这可能作为一种预测性生物标志物和潜在的治疗靶点。
