长链非编码 RNA LINC01234 通过海绵吸附 miR-204-5p 调控 CBFB 表达在胃癌中发挥竞争性内源 RNA 的作用。
Long Noncoding RNA LINC01234 Functions as a Competing Endogenous RNA to Regulate CBFB Expression by Sponging miR-204-5p in Gastric Cancer.
机构信息
Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
出版信息
Clin Cancer Res. 2018 Apr 15;24(8):2002-2014. doi: 10.1158/1078-0432.CCR-17-2376. Epub 2018 Jan 31.
Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases, including cancers. However, the overall biological roles and clinical significance of most lncRNAs in gastric carcinogenesis are not fully understood. We investigated the clinical significance, biological function, and mechanism of LINC01234 in gastric cancer. First, we analyzed LINC01234 alterations in gastric cancerous and noncancerous tissues through an analysis of sequencing data obtained from The Cancer Genome Atlas. Next, we evaluated the effect of LINC01234 on the gastric cancer cell proliferation and apoptosis, and its regulation of miR-204-5p by acting as a competing endogenous RNA (ceRNA). The animal model was used to support the experimental findings. We found that LINC01234 expression was significantly upregulated in gastric cancer tissues and was associated with larger tumor size, advanced TNM stage, lymph node metastasis, and shorter survival time. Furthermore, knockdown of LINC01234-induced apoptosis and growth arrest and inhibited tumorigenesis in mouse xenografts. Mechanistic investigations indicated that LINC01234 functioned as a ceRNA for miR-204-5p, thereby leading to the derepression of its endogenous target core-binding factor β (CBFB). LINC01234 is significantly overexpressed in gastric cancer, and LINC01234-miR-204-5p-CBFB axis plays a critical role in gastric cancer tumorigenesis. Our findings may provide a potential new target for gastric cancer diagnosis and therapy. .
长链非编码 RNA(lncRNA)已成为多种人类疾病(包括癌症)的重要调控因子。然而,大多数 lncRNA 在胃癌发生中的整体生物学作用和临床意义尚不完全清楚。我们研究了 LINC01234 在胃癌中的临床意义、生物学功能和机制。首先,我们通过分析来自癌症基因组图谱的测序数据,分析了 LINC01234 在胃癌组织和非癌组织中的改变。接下来,我们评估了 LINC01234 对胃癌细胞增殖和凋亡的影响,以及其通过作为竞争内源 RNA(ceRNA)来调节 miR-204-5p 的作用。动物模型用于支持实验结果。我们发现 LINC01234 在胃癌组织中的表达明显上调,与肿瘤较大、TNM 分期较晚、淋巴结转移和生存期较短有关。此外,LINC01234 的敲低诱导了凋亡和生长停滞,并抑制了小鼠异种移植中的肿瘤发生。机制研究表明,LINC01234 作为 miR-204-5p 的 ceRNA,从而导致其内源性靶基因核心结合因子 β(CBFB)的去抑制。LINC01234 在胃癌中显著过表达,LINC01234-miR-204-5p-CBFB 轴在胃癌肿瘤发生中起着关键作用。我们的研究结果可能为胃癌的诊断和治疗提供了一个潜在的新靶点。