Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Cell Biology, Key Laboratory of Cell Biology of Ministry of Public Health, and Key Laboratory of Medical Cell Biology of Ministry of Education, China Medical University, Shenyang, Liaoning, China.
Aging (Albany NY). 2020 Nov 18;12(24):25060-25075. doi: 10.18632/aging.103979.
Although the anomalous expression of long non-coding RNAs (lncRNAs) has been extensively investigated in numerous carcinomas including gastric cancer (GC), their function remains unclear. The aim of our study was to explore the role of LINC01235 in GC. We used real-time quantitative PCR (RT-qPCR) to measure the expression of LINC01235 and twist family bHLH transcription factor 2 (TWIST2) in GC tissues. Scratch and transwell assays were performed to evaluate cellular capacity for migration and invasion. Gene relationships were explored by Weighted Gene Co-Expression Network Analysis (WGCNA). We measured TWIST2, thrombospondin 2 (THBS2) and epithelial-mesenchymal transition (EMT)-related proteins with western blot. We also used Pearson correlation analysis and the Kaplan-Meier method to detect associations among genes and overall survival. We found that LINC01235 was upregulated in GC tissues and cells. LINC01235 down-regulation restricted migration and invasion. Interestingly, we found the LINC01235-TWIST2-THBS2 axis induced EMT. Additionally, TWIST2 upregulated LINC01235 transcription in luciferase and chromatin immunoprecipitation (ChIP) assays. Bioinformatics analysis showed that microRNA (miR)-6852-5p might be a key gene involved in the regulation of TWIST2 by LINC01235. The LINC01235-TWIST2 positive feedback loop mainly affected migration and invasion of GC cells, which suggests it may serve as a potential therapeutic target in gastric cancer.
虽然长链非编码 RNA（lncRNAs）的异常表达已在包括胃癌（GC）在内的许多癌中得到广泛研究，但它们的功能仍不清楚。我们的研究旨在探索 LINC01235 在 GC 中的作用。我们使用实时定量 PCR（RT-qPCR）测量 GC 组织中 LINC01235 和扭曲家族 bHLH 转录因子 2（TWIST2）的表达。划痕和 Transwell 测定用于评估细胞迁移和侵袭能力。通过加权基因共表达网络分析（WGCNA）探索基因关系。我们使用 Western blot 测量 TWIST2、血小板反应蛋白 2（THBS2）和上皮-间充质转化（EMT）相关蛋白。我们还使用 Pearson 相关分析和 Kaplan-Meier 方法检测基因与总生存期之间的关联。我们发现 LINC01235 在 GC 组织和细胞中上调。LINC01235 下调限制了迁移和侵袭。有趣的是，我们发现 LINC01235-TWIST2-THBS2 轴诱导 EMT。此外，TWIST2 在荧光素酶和染色质免疫沉淀（ChIP）测定中转录上调 LINC01235。生物信息学分析表明，微小 RNA（miR）-6852-5p 可能是涉及 LINC01235 调节 TWIST2 的关键基因。LINC01235-TWIST2 正反馈回路主要影响 GC 细胞的迁移和侵袭，这表明它可能是胃癌的潜在治疗靶点。
