下调 circRNA_0044516 通过 miR-149/Wnt1/β-catenin 通路抑制胃癌细胞增殖。
Downregulating circRNA_0044516 Inhibits Cell Proliferation in Gastric Cancer Through miR-149/Wnt1/β-catenin Pathway.
机构信息
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, NO. 218 Jixi Rd, Hefei, 230022, Anhui Province, China.
出版信息
J Gastrointest Surg. 2021 Jul;25(7):1696-1705. doi: 10.1007/s11605-020-04834-w. Epub 2020 Nov 2.
BACKGROUND
Circular RNAs (circRNAs) play important roles in the progression of gastric cancer (GC). The Wnt1/β-catenin pathway can promote the proliferation of GC cells. This study aimed to explore whether circRNA_0044516 can regulate the proliferation of GC cells by modulating the Wnt1/β-catenin pathway.
METHODS
The expression of circRNA_0044516, miR-149, Wnt1, and β-catenin in GC tissues or cells was detected by qRT-PCR and western blot. Cell viability and apoptosis were measured by CCK-8 and flow cytometry assays, respectively. The interaction between circRNA_0044516 and miR-149 was determined by luciferase reporter and RNA pull-down assays.
RESULTS
Upregulated circRNA_0044516 was found in GC tissues and cell lines. Downregulating circRNA_0044516 inhibited the viability and promoted apoptosis of GC cells. CircRNA_0044516 targeted miR-149, and its downregulation elevated miR-149 level in GC cells. Mechanistically, silencing circRNA_0044516 reduced the protein level of Wnt1 and β-catenin through miR-149, and finally suppressed viability and contributed to apoptosis of GC cells. Moreover, circRNA_0044516 knockdown inhibited the tumor growth of HGC-27 cells in nude mice.
CONCLUSIONS
Our results indicated an important role of circRNA_0044516 in GC and elucidated that downregulation of circRNA_0044516 inhibits the proliferation of GC cells through miR-149/Wnt1/β-catenin.
背景
环状 RNA（circRNAs）在胃癌（GC）的进展中发挥重要作用。Wnt1/β-catenin 通路可以促进 GC 细胞的增殖。本研究旨在探讨 circRNA_0044516 是否可以通过调节 Wnt1/β-catenin 通路来调节 GC 细胞的增殖。
方法
通过 qRT-PCR 和 Western blot 检测 GC 组织或细胞中 circRNA_0044516、miR-149、Wnt1 和 β-catenin 的表达。通过 CCK-8 和流式细胞术分别测定细胞活力和凋亡。通过荧光素酶报告和 RNA 下拉测定确定 circRNA_0044516 与 miR-149 之间的相互作用。
结果
在 GC 组织和细胞系中发现上调的 circRNA_0044516。下调 circRNA_0044516 抑制 GC 细胞的活力并促进其凋亡。circRNA_0044516 靶向 miR-149，下调其在 GC 细胞中的水平。在机制上，沉默 circRNA_0044516 通过 miR-149 降低 Wnt1 和 β-catenin 的蛋白水平，最终抑制 GC 细胞的活力并促进其凋亡。此外，circRNA_0044516 敲低抑制裸鼠中 HGC-27 细胞的肿瘤生长。
结论
我们的结果表明 circRNA_0044516 在 GC 中起重要作用，并阐明下调 circRNA_0044516 通过 miR-149/Wnt1/β-catenin 抑制 GC 细胞的增殖。
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