Chang Ya-Sian, Lee Ya-Ting, Yen Ju-Chen, Chang Yuli C, Lin Li-Li, Chan Wen-Ling, Chang Wei-Chiao, Lin Shyr-Yi, Chang Jan-Gowth
Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan.
Center for Precision Medicine, China Medical University Hospital, Taichung, Taiwan.
Front Oncol. 2021 Sep 20;11:592045. doi: 10.3389/fonc.2021.592045. eCollection 2021.
Long noncoding RNA (lncRNA) mediates the pathogenesis of various diseases, including cancer and cardiovascular, infectious, and metabolic diseases. This study examined the role of lncRNA in the development and progression of cancer.
The expression of was determined using tissues containing complementary DNA (cDNA) from patients with liver, lung, kidney, oral, and colon cancers. The expression of acting genes adjacent to the locus (, , , , , , and ) was also assessed. We used knockdown and chromatin immunoprecipitation (ChIP) assays to identify the acting genes that interact with .
was most significantly downregulated in hepatocellular carcinoma (HCC), while a higher level correlated with a shorter survival time of patients with HCC. Multivariate analysis indicated was not an independent predictor for overall survival. was significantly upregulated, and its increased expression was associated with dismal survival in HCC patients, similar to the results for . knockdown significantly decreased cellular migration. ChIP of HCC cell lines revealed that is regulated by the transcription factor ATF3 and binds to the promoter the activated complex. Additionally, when was knocked down, the expression of target genes such as , , and was also downregulated. could play a positive or negative regulator for with a context-dependent manner in both HCC tissues and animal model.
Our study suggests that plays a key role in HCC progression -regulated target genes and may serve as a novel therapeutic target.
长链非编码RNA(lncRNA)介导包括癌症、心血管疾病、传染病和代谢疾病在内的多种疾病的发病机制。本研究探讨了lncRNA在癌症发生发展中的作用。
使用来自肝癌、肺癌、肾癌、口腔癌和结肠癌患者的含互补DNA(cDNA)的组织来测定[具体lncRNA名称未给出]的表达。还评估了与[具体lncRNA名称未给出]基因座相邻的作用基因([列举的多个基因名称未给出])的表达。我们使用敲低和染色质免疫沉淀(ChIP)试验来鉴定与[具体lncRNA名称未给出]相互作用的作用基因。
[具体lncRNA名称未给出]在肝细胞癌(HCC)中下调最为显著,而较高的[具体lncRNA名称未给出]水平与HCC患者较短的生存时间相关。多变量分析表明[具体lncRNA名称未给出]不是总生存的独立预测因子。[另一个具体lncRNA名称未给出]显著上调,其表达增加与HCC患者的不良生存相关,与[具体lncRNA名称未给出]的结果相似。[具体lncRNA名称未给出]敲低显著降低细胞迁移。HCC细胞系的ChIP显示[具体lncRNA名称未给出]受转录因子ATF3调控,并与[具体基因名称未给出]启动子结合形成活化复合物。此外,但[具体lncRNA名称未给出]被敲低时,[具体lncRNA名称未给出]的靶基因如[列举的多个基因名称未给出]的表达也下调。在HCC组织和动物模型中,[具体lncRNA名称未给出]可能以上下文依赖的方式对[具体lncRNA名称未给出]发挥正向或负向调节作用。
我们的研究表明[具体lncRNA名称未给出]在HCC进展中通过调控靶基因发挥关键作用,可能成为一个新的治疗靶点。