circ-CEP85L suppresses the proliferation and invasion of gastric cancer by regulating NFKBIA expression via miR-942-5p
circ-CEP85L suppresses the proliferation and invasion of gastric cancer by regulating NFKBIA expression via miR-942-5p
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DOI：
10.1002/jcp.29556
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发表时间：
2020-02-05
影响因子：
5.6
通讯作者：
Li, Ping
中科院分区：
文献类型：
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作者：
Lu, Jun;Wang, Yao-hui;Li, Ping
环状RNA（circular RNA，circRNA）在胃癌发病机制中的作用及其表达模式尚未完全阐明。在这项研究中，我们确定了差异表达的circRNA的circRNA芯片，并验证了定量逆转录聚合酶链反应的结果，使用117个临床样本。进行细胞计数试剂盒-8、伤口愈合、Transwell和肿瘤球形成测定以评估circ-CEP 85 L对体外细胞增殖和侵袭的影响。小鼠腹腔注射模型用于评估circ-CEP 85 L在体内的功能。进行荧光素酶报告基因测定、荧光原位杂交和拯救实验以阐明circ-CEP 85 L的潜在机制。我们发现，circ-CEP 85 L，这还没有在GC中研究，是显着下调GC组织中，减少circ-CEP 85 L的表达与预后不良显着相关。circ-CEP 85 L的敲低促进了胃癌细胞的增殖和侵袭，而circ-CEP 85 L的过表达则逆转了这一作用。此外，抑制circ-CEP 85 L促进体内肿瘤生长。在机制上，证实circ-CEP 85 L是miR-942- 5 p的直接靶标。此外，拯救实验表明，circ-CEP 85 L能够通过海绵状miR-942- 5 p抑制GC细胞的增殖和侵袭。最后，蛋白质印迹分析证实miR-942- 5 p的下调有效地逆转了由circ-CEP 85 L过表达诱导的NFKBIA的抑制。因此，我们得出结论，circ-CEP 85 L通过充当miR-942- 5 p的海绵来促进NFKBIA表达;从而抑制GC增殖和侵袭。circ-CEP 85 L是治疗胃癌的潜在靶点。
The expression pattern and role of circular RNAs (circRNAs) in the pathogenesis of gastric cancer (GC) and their underlying mechanisms remain unresolved. In this study, we identified differentially expressed circRNAs by a circRNA microarray and verified the results by quantitative reverse transcription-polymerase chain reaction using 117 clinical samples. Cell Counting Kit-8, wound healing, Transwell, and tumorsphere formation assays were conducted to assess the effects of circ-CEP85L on cell proliferation and invasion in vitro. Mouse intraperitoneal injection models were used to assess the functions of circ-CEP85L in vivo. Luciferase reporter assays, fluorescence in situ hybridization, and rescue experiments were performed to elucidate the underlying mechanism of circ-CEP85L. We found that circ-CEP85L, which has not been studied in GC, was significantly downregulated in GC tissues and that decreased circ-CEP85L expression correlated significantly with a worse prognosis. The knockdown of circ-CEP85L promoted the proliferation and invasion of GC cells, which was reversed by overexpression of circ-CEP85L. Furthermore, inhibition of circ-CEP85L promoted tumor growth in vivo. Mechanistically, circ-CEP85L was confirmed to be a direct target of miR-942-5p. In addition, rescue experiments indicated that circ-CEP85L is able to inhibit the proliferation and invasion of GC cells by sponging miR-942-5p. Finally, western blot assays verified that the downregulation of miR-942-5p efficiently reversed the inhibition of NFKBIA induced by circ-CEP85L overexpression. Therefore, we conclude that circ-CEP85L promotes NFKBIA expression by acting as a sponge of miR-942-5p; thus, inhibiting GC proliferation and invasion. circ-CEP85L is a potential target in the treatment of GC.