Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China.
Department of Gynecology reported and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin Province, China.
Biomed Pharmacother. 2020 Apr;124:109848. doi: 10.1016/j.biopha.2020.109848. Epub 2020 Jan 23.
Gastric cancer (GC) is the most prevailing malignant tumor of digestive tract and accounts for a considerable part of cancer-relevant deaths worldwide. An increasing number of literatures highlight the important role of lncRNAs in the occurrence and development of GC. Considering that the function of RHPN1-AS1 in GC remains to be fully inquired, we purposed to investigate the potential and mechanism of RHPN1-AS1 in GC. The expression of RHPN1-AS1 was significantly upregulated in GC samples and cells. High RHPN1-AS1 level was strongly correlated with advanced stages of GC and predicted poor outcomes of GC. Furthermore, depletion of RHPN1-AS1 inhibited cell proliferation and cell cycle whereas promoted cell apoptosis. Subcellular fractionation analysis expounded the main expression of RHPN1-AS1 in GC cell cytoplasm. Herein, we conjectured that RHPN1-AS1 might exert its performance in GC through the ceRNA network. Our findings demonstrated that RHPN1-AS1 enhanced ETS1 expression via sponging miR-1299. More importantly, the transcriptional activation of RHPN1-AS1 was mediated by ETS1. Results of recue assays validated that RHPN1-AS1/miR-1299/ETS1 positive feedback loop aggravated the malignant behaviors of GC, revealing RHPN1-AS1 as a latent effective target for the treatment of GC patients.
胃癌(GC)是最常见的消化道恶性肿瘤,在全球癌症相关死亡中占相当大的比例。越来越多的文献强调了长链非编码 RNA(lncRNAs)在 GC 发生和发展中的重要作用。考虑到 RHPN1-AS1 在 GC 中的功能仍有待充分研究,我们旨在探讨 RHPN1-AS1 在 GC 中的潜在作用和机制。RHPN1-AS1 在 GC 样本和细胞中的表达明显上调。高 RHPN1-AS1 水平与 GC 的晚期阶段强烈相关,并预测 GC 的预后不良。此外,RHPN1-AS1 的耗竭抑制了细胞增殖和细胞周期,而促进了细胞凋亡。亚细胞分馏分析阐述了 RHPN1-AS1 在 GC 细胞质中的主要表达。因此,我们推测 RHPN1-AS1 可能通过 ceRNA 网络在 GC 中发挥作用。我们的研究结果表明,RHPN1-AS1 通过海绵 miR-1299 增强了 ETS1 的表达。更重要的是,RHPN1-AS1 的转录激活是由 ETS1 介导的。挽救实验的结果验证了 RHPN1-AS1/miR-1299/ETS1 正反馈环加重了 GC 的恶性行为,表明 RHPN1-AS1 是治疗 GC 患者的潜在有效靶点。