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RHPN1-AS1/miR-1299/ETS1 的正反馈环加速了胃癌的恶化。

The positive feedback loop of RHPN1-AS1/miR-1299/ETS1 accelerates the deterioration of gastric cancer.

机构信息

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.

出版信息

Biomed Pharmacother. 2020 Apr;124:109848. doi: 10.1016/j.biopha.2020.109848. Epub 2020 Jan 23.

Abstract

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.

摘要

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。

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