环状RNA_100290通过miR-29b-3p/整合素α11轴促进胃癌细胞增殖和侵袭，并受真核翻译起始因子4A3调控。
CircRNA_100290 promotes GC cell proliferation and invasion via the miR-29b-3p/ITGA11 axis and is regulated by EIF4A3.
作者信息
Wang Gang, Sun Dan, Li Wenhui, Xin Yan
机构信息
Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, Liaoning Province, China.
Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, 16766 Jingshi Road, Lixia District, Jinan, Shandong Province, China.
出版信息
Cancer Cell Int. 2021 Jun 28;21(1):324. doi: 10.1186/s12935-021-01964-2.
BACKGROUND
Circular RNAs (circRNAs) have been reported to be important regulators of the development and progression of various carcinomas. However, the role of circRNA_100290 in gastric cancer (GC) is still unclear. This study aimed to investigate the role of circRNA_100290 in GC invasion and metastasis and the possible underlying mechanism.
METHODS
The expression of circRNA_100290 in GC cells and tissues was examined using quantitative real-time polymerase chain reaction (qRT-PCR). The role of circRNA_100290 in cell proliferation, migration, and invasion was evaluated in the AGS and HGC-27 cell lines in vitro. Bioinformatics tools, dual-luciferase reporter assays, Western blot assays and qRT-PCR were used to explore the pathways downstream of circRNA_100290. The mechanism underlying the regulation of circRNA_100290 expression was explored using RNA immunoprecipitation, qRT-PCR, and Western blot assays.
RESULTS
The expression of circRNA_100290 was significantly upregulated in GC cells and 102 GC tissues, and high circRNA_100290 expression in GC was closely related to Borrmann's type, lymph node metastasis and tumour-node-metastasis stage. In vitro, knockdown of circRNA_100290 in AGS and HGC-27 cells significantly inhibited cell proliferation, migration, and invasion. Mechanistically, a dual-luciferase reporter assay confirmed the direct interaction between circRNA_100290 and miR-29b-3p, which targets ITGA11, an oncogene that is closely related to epithelial-mesenchymal transition (EMT). In addition, EIF4A3, an RNA-binding protein (RBP), could inhibit the formation of circRNA_100290 by binding to the flanking sites of circRNA_100290. Low EIF4A3 expression in GC was related to a poor prognosis.
CONCLUSIONS
Elevated circRNA_100290 expression in GC promotes cell proliferation, invasion and EMT via the miR-29b-3p/ITGA11 axis and might be regulated by EIF4A3. CircRNA_100290 might be a promising biomarker and target for GC therapy.
背景
环状RNA（circRNAs）已被报道为多种癌症发生发展的重要调节因子。然而，circRNA_100290在胃癌（GC）中的作用仍不清楚。本研究旨在探讨circRNA_100290在GC侵袭和转移中的作用及其潜在机制。
方法
采用定量实时聚合酶链反应（qRT-PCR）检测circRNA_100290在GC细胞和组织中的表达。在体外AGS和HGC-27细胞系中评估circRNA_100290在细胞增殖、迁移和侵袭中的作用。使用生物信息学工具、双荧光素酶报告基因检测、蛋白质免疫印迹分析和qRT-PCR来探索circRNA_100290的下游通路。通过RNA免疫沉淀、qRT-PCR和蛋白质免疫印迹分析来探索circRNA_100290表达调控的机制。
结果
circRNA_100290在GC细胞和102例GC组织中表达显著上调，且GC中circRNA_100290的高表达与Borrmann分型、淋巴结转移和肿瘤-淋巴结-转移分期密切相关。在体外，敲低AGS和HGC-27细胞中的circRNA_100290可显著抑制细胞增殖、迁移和侵袭。机制上，双荧光素酶报告基因检测证实了circRNA_100290与miR-29b-3p之间的直接相互作用，miR-29b-3p靶向ITGA11，ITGA11是一种与上皮-间质转化（EMT）密切相关的癌基因。此外，RNA结合蛋白（RBP）EIF4A3可通过与circRNA_100290的侧翼位点结合来抑制circRNA_100290的形成。GC中EIF4A3低表达与预后不良相关。
结论
GC中circRNA_100290表达升高通过miR-29b-3p/ITGA11轴促进细胞增殖、侵袭和EMT，且可能受EIF4A3调控。circRNA_100290可能是一种有前景的GC生物标志物和治疗靶点。
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