Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No.136 Jingzhou Street, Xiangcheng District, Xiangyang City, 441000, Hubei Province, China.
Mol Biotechnol. 2024 Dec;66(12):3583-3596. doi: 10.1007/s12033-023-00958-x. Epub 2023 Dec 19.
Gastric cancer (GC) is a malignant tumor with the highest incidence among all kinds of malignant tumors in China. Long noncoding RNAs (LncRNAs) have been reported to act as microRNA (miRNAs) sponges and thus play key roles in biological processes and pathogenesis. Thus, this study aimed to investigate the functional effects and the regulatory mechanism of lncRNA opa interacting protein 5-antisense 1 (OIP5-AS1) in gastric cancer cells. The expression of OIP5-AS1, miR-140-5p, Ubiquitin protein ligase E3 component n-recognin 5 (UBR5) was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration, and invasion were assessed using Cell-Counting Kit-8 (CCK-8), Flow cytometry, and Transwell assays. UBR5 protein level was detected by Western blot. Binding between miR-140-5p and OIP5-AS1 or UBR5 was predicted by Starbasev2.0 and TargetScan, and verified using Dual-luciferase reporter assays and RNA pull-down assay. A xenograft mice model was used to evaluate the effects of OIP5-AS1 on tumor growth in vivo. OIP5-AS1 was upregulated in GC cancer and cells. OIP5-AS1 knockdown inhibited cell proliferation, migration, invasion, but induced cell apoptosis in GC. In mechanism, OIP5-AS1 might serve as a sponge for miR-140-5p to enhance UBR5 expression. Moreover, overexpression of miR-140-5p or UBR5 partly reversed the effects of OIP5-AS1 depletion on the progression of GC cells. Furthermore, OIP5-AS1 depletion also suppressed tumor growth in vivo. OIP5-AS1 silencing might suppress proliferation, migration, invasion, and induced apoptosis in GC cells by regulating the miR-140-5p/UBR5 axis.
胃癌（GC）是中国各种恶性肿瘤中发病率最高的恶性肿瘤。长链非编码 RNA（LncRNA）已被报道可作为 microRNA（miRNA）的海绵，从而在生物过程和发病机制中发挥关键作用。因此，本研究旨在探讨 lncRNA opa 相互作用蛋白 5-反义 1（OIP5-AS1）在胃癌细胞中的功能作用和调控机制。采用实时定量聚合酶链反应（qRT-PCR）检测 OIP5-AS1、miR-140-5p、泛素蛋白连接酶 E3 成分 n-识别蛋白 5（UBR5）的表达。采用细胞计数试剂盒-8（CCK-8）、流式细胞术和 Transwell 检测细胞增殖、凋亡、迁移和侵袭。采用 Western blot 检测 UBR5 蛋白水平。通过 Starbasev2.0 和 TargetScan 预测 miR-140-5p 与 OIP5-AS1 或 UBR5 的结合，并用双荧光素酶报告基因检测和 RNA 下拉实验验证。利用异种移植小鼠模型评估 OIP5-AS1 对体内肿瘤生长的影响。GC 癌和细胞中 OIP5-AS1 上调。OIP5-AS1 敲低抑制 GC 细胞增殖、迁移和侵袭，但诱导细胞凋亡。在机制上，OIP5-AS1 可能作为 miR-140-5p 的海绵，增强 UBR5 的表达。此外，miR-140-5p 或 UBR5 的过表达部分逆转了 OIP5-AS1 耗竭对 GC 细胞进展的影响。此外，OIP5-AS1 耗竭也抑制了体内肿瘤的生长。OIP5-AS1 沉默可能通过调节 miR-140-5p/UBR5 轴抑制 GC 细胞的增殖、迁移、侵袭和诱导凋亡。
