Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Wuhan, Hubei, China.
Bioengineered. 2021 Dec;12(1):8793-8808. doi: 10.1080/21655979.2021.1983974.
Circular RNAs (circRNAs) are RNA molecules that do not encode proteins but are known to regulate tumor progression. This study was designed to explore the underlying mechanism driving circRNA-mediated modulation of gastric cancer (GC). Bioinformatics analysis of gene chip GSE83521 was used to identify multiple circRNAs that were differentially regulated in matched GC and adjacent normal tissues. The circRNA with the largest variation in expression (hsa_circ_0000751) was selected for further examination. The expression profile of hsa_circ_0000751 and its target-specific interactions with microRNAs (miRNAs) and downstream gene transcripts were determined using quantitative real-time polymerase chain reaction, luciferase reporter assays, and rescue assays in human tissues and cells. The relationship between hsa_circ_0000751 expression and the clinicopathological parameters of 25 GC patients was analyzed. Furthermore, ubiquinol-cytochrome c reductase core protein 2 (UQCRC2), a GC suppressor, was detected via western blot analysis. The results showed that hsa_circ_0000751 levels were markedly downregulated in GC tissues and cell lines, which were also inversely proportional to the stage of tumor-node-metastasis (TNM) classification, tumor volume, and lymph node metastasis in GC patients. Conversely, hsa_circ_0000751 overexpression suppressed tumor progression, migration, and invasion and . From our results, we showed that hsa_circ_0000751 may serve as a miRNA sponge to suppress the activity of miR-488, thereby increasing the expression of the miR-488-target gene, UQCRC2, and limiting GC progression. Given its negative regulation of oncogenic miRNAs, the hsa_circ_0000751/miR-488/UQCRC2 axis may be crucial in the development of novel GC therapies.
环状 RNA（circRNAs）是一种不编码蛋白质的 RNA 分子，但已知其可调节肿瘤的进展。本研究旨在探讨驱动环状 RNA 介导的胃癌（GC）调节的潜在机制。使用基因芯片 GSE83521 的生物信息学分析来鉴定在匹配的 GC 和相邻正常组织中差异调节的多个环状 RNA。选择表达变化最大的环状 RNA（hsa_circ_0000751）进行进一步检查。使用定量实时聚合酶链反应、荧光素酶报告测定和在人组织和细胞中的挽救测定来确定 hsa_circ_0000751 的表达谱及其与 microRNAs（miRNAs）和下游基因转录物的靶特异性相互作用。分析了 25 例 GC 患者 hsa_circ_0000751 表达与临床病理参数的关系。此外，通过 Western blot 分析检测了泛醌-细胞色素 c 还原酶核心蛋白 2（UQCRC2），一种 GC 抑制剂。结果表明，hsa_circ_0000751 水平在 GC 组织和细胞系中明显下调，并且与 GC 患者的 TNM 分类、肿瘤体积和淋巴结转移的阶段呈反比。相反，hsa_circ_0000751 的过表达抑制了肿瘤的进展、迁移和侵袭。从我们的结果来看，hsa_circ_0000751 可能作为 miRNA 的海绵来抑制 miR-488 的活性，从而增加 miR-488 靶基因 UQCRC2 的表达，并限制 GC 的进展。鉴于其对致癌 miRNA 的负调控，hsa_circ_0000751/miR-488/UQCRC2 轴可能在新型 GC 治疗的开发中至关重要。
