Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Anatomy, Histology and Embryology, Research Centre for Bone and Stem Cells, Nanjing Medical University, Nanjing, China.
Cell Death Dis. 2018 Jun 18;9(7):717. doi: 10.1038/s41419-018-0758-8.
Substantial evidence shows that long non-coding RNAs (lncRNAs) participate in many biological mechanisms, and their dysregulation are also involved in the development and progression of cancers, including gastric cancer (GC). Long intergenic non-coding RNA 00324 (LINC00324), a 2115 bp ncRNA, is located on chromosome 17p13.1. The biological function and molecular mechanisms of LINC00324 in GC remains undiscovered. In this paper, we found that the expression level of LINC00324 was significantly upregulated in GC tissues compared with the corresponding normal tissues. The overexpression of LINC00324 was correlated with advanced TNM stage, larger tumor size, and lymph node metastasis as well as poor prognosis. Further experiments revealed that knockdown of LINC00324 could suppress the proliferation of GC cells. RNA transcriptome sequencing technology revealed that FAM83B may be a significant downstream target gene of LINC00324. LINC00324 could combine with the RNA-binding protein (RBP) human antigen R (HuR) and thus stabilize the expression of FAM83B. Moreover, rescue assays showed that the reduced FAM83B expression partially reversed the promotion of cell growth in GC induced by the overexpression of LINC00324. In conclusion, our study revealed that LINC00324 acted as an oncogene in tumorigenesis and progression, suggesting that it could be a new biomarker in diagnosis and prognosis of GC.
大量证据表明，长非编码 RNA（lncRNA）参与许多生物学机制，其失调也与癌症的发展和进展有关，包括胃癌（GC）。长基因间非编码 RNA 00324（LINC00324）是一种 2115bp 的 ncRNA，位于 17p13.1 号染色体上。LINC00324 在 GC 中的生物学功能和分子机制尚不清楚。在本文中，我们发现 LINC00324 在 GC 组织中的表达水平明显高于相应的正常组织。LINC00324 的过表达与较晚的 TNM 分期、较大的肿瘤大小、淋巴结转移以及不良预后相关。进一步的实验表明，敲低 LINC00324 可以抑制 GC 细胞的增殖。RNA 转录组测序技术显示，FAM83B 可能是 LINC00324 的一个重要下游靶基因。LINC00324 可以与 RNA 结合蛋白（RBP）人抗原 R（HuR）结合，从而稳定 FAM83B 的表达。此外，挽救实验表明，下调 FAM83B 的表达部分逆转了 LINC00324 过表达诱导的 GC 细胞生长促进作用。综上所述，本研究表明 LINC00324 在肿瘤发生和进展中起癌基因作用，提示其可能成为 GC 诊断和预后的新标志物。
