National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China.
Oncogene. 2018 Aug;37(33):4505-4517. doi: 10.1038/s41388-018-0266-4. Epub 2018 May 10.
Recently, long noncoding RNAs (lncRNAs) have been reported to play a pivotal role in the occurrence and progression of cancer because of their unique characteristics and have therefore become an active area of cancer research. The object of this study was to screen lncRNAs that are dysregulated in gastric cancer and to investigate their potential functions. Global expression of lncRNAs in gastric cancer and adjacent normal tissues of patients was profiled using a microarray assay. We identified an lncRNA (GALNT5 uaRNA, UTR-associated RNA) that is derived from the 3'-UTR of GALNT5. This lncRNA was transcribed independently of the coding region of GALNT5 and was determined to be markedly upregulated in human gastric carcinoma relative to their corresponding normal gastric tissues by quantitative RT-PCR (qRT-PCR) analysis of tissues from 122 gastric carcinoma patients. The expression of GALNT5 uaRNA was significantly correlated with the TNM stage and with lymph node metastasis. Further results demonstrated that GALNT5 uaRNA facilitated the proliferation and migration of gastric cancer cells in vitro and promoted tumor growth in a mouse model of human gastric cancer. Our results also indicated that GALNT5 uaRNA might function in gastric cancer by binding with HSP90. Further studies indicated that the 5'-end stem-loop motifs of GALNT5 uaRNA promoted the binding of HSP90 and its client proteins, and thus inhibited ubiquitination of the clients. These results expanded our understanding of GALNT5 uaRNA as a new avenue for therapeutic intervention against gastric cancer progression.
最近，长链非编码 RNA（lncRNA）因其独特的特性被报道在癌症的发生和发展中发挥关键作用，因此成为癌症研究的一个活跃领域。本研究的目的是筛选胃癌中失调的 lncRNA，并研究其潜在功能。我们使用微阵列分析对胃癌患者和相邻正常组织中的 lncRNA 进行了全局表达谱分析。我们鉴定了一种来自 GALNT5 3'UTR 的 lncRNA（GALNT5 uaRNA，UTR 相关 RNA）。通过对 122 例胃癌患者组织的定量 RT-PCR（qRT-PCR）分析，发现这种 lncRNA与编码区无关，在人胃癌中明显上调。GALNT5 uaRNA 的表达与 TNM 分期和淋巴结转移显著相关。进一步的结果表明，GALNT5 uaRNA 在体外促进胃癌细胞的增殖和迁移，并在人胃癌小鼠模型中促进肿瘤生长。我们的结果还表明，GALNT5 uaRNA 可能通过与 HSP90 结合在胃癌中发挥作用。进一步的研究表明，GALNT5 uaRNA 的 5'端茎环结构促进了 HSP90 与其客户蛋白的结合，从而抑制了客户蛋白的泛素化。这些结果扩展了我们对 GALNT5 uaRNA 的理解，为治疗干预胃癌进展提供了新途径。
