Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Bioengineered. 2022 May;13(5):12326-12337. doi: 10.1080/21655979.2022.2073001.
The treatment of gastric cancer (GC) is extremely challenging; however, the specific pathogenesis of GC remains unclear. Circular RNAs (CircRNAs) are non-coding RNAs that can regulate gene expression both transcriptionally and post-transcriptionally. However, little is known about the circRNAs that are important in the progression of GC. This study identified significantly dysregulated circRNAs by analyzing gastric cancer patients and normal control tissues. The target gene was predicted using online bioinformatics tools and verified using RNA pull-down and luciferase reporter assays. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to evaluate gene and protein expression. The malignant behavior of GC cells was determined using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, wound healing assay, Transwell invasion assay, and flow cytometry. CircPFKP is downregulated in GC tissues, and overexpression of circPFKP inhibits malignant behavior in GC cells. Bioinformatics predicted that circPFKP could bind to miR-644, and miR-644 could target disintegrin-like and metalloprotease domain-containing thrombospondin type 1 motif-like 5 (ADAMTSL5). Overexpression of circPFKP enhances the expression of ADAMTSL5 by decreasing the expression of miR-644 to suppress the growth of xenograft GC tumors in vivo and in vitro. In conclusion, the circPFKP/miR-644/ADAMTSL5 regulatory pathway inhibited the malignant progression of GC. These findings may extend our understanding of the effects of circRNAs on cancer development and provide novel targets for the diagnosis of GC.
胃癌（GC）的治疗极具挑战性；然而，GC 的具体发病机制仍不清楚。环状 RNA（circRNA）是非编码 RNA，可在转录和转录后水平调节基因表达。然而，对于在 GC 进展中起重要作用的 circRNA 知之甚少。本研究通过分析胃癌患者和正常对照组织，鉴定出显著失调的 circRNA。使用在线生物信息学工具预测靶基因，并通过 RNA 下拉和荧光素酶报告基因检测进行验证。采用实时定量聚合酶链反应（qRT-PCR）和 Western blot 检测基因和蛋白表达。通过 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐（MTT）测定、划痕愈合试验、Transwell 侵袭试验和流式细胞术评估 GC 细胞的恶性行为。CircPFKP 在 GC 组织中下调，过表达 circPFKP 抑制 GC 细胞的恶性行为。生物信息学预测 circPFKP 可以与 miR-644 结合，miR-644 可以靶向解整合素样金属蛋白酶域 10（ADAMTSL10）。circPFKP 通过降低 miR-644 的表达来增强 ADAMTSL5 的表达，从而抑制体内和体外异种移植 GC 肿瘤的生长。总之，circPFKP/miR-644/ADAMTSL5 调控通路抑制了 GC 的恶性进展。这些发现可能扩展了我们对 circRNA 对癌症发展影响的理解，并为 GC 的诊断提供了新的靶点。
