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.

译文

环状rna (circRNAs) 在胃癌 (GC) 发病中的表达模式和作用及其潜在机制仍未解决。在这项研究中,我们通过circRNA微阵列鉴定了差异表达的circRNA,并使用117临床样品通过定量逆转录-聚合酶链反应验证了结果。进行细胞计数试剂盒-8,伤口愈合,Transwell和肿瘤球形成试验,以评估circ-CEP85L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体内circ-CEP85L的功能。进行了荧光素酶报告基因测定,荧光原位杂交和抢救实验,以阐明circ-CEP85L的潜在机制。我们发现,尚未在GC中进行研究的circ-CEP85L在GC组织中被显着下调,并且circ-CEP85L表达的降低与预后差显着相关。circ-CEP85L的敲除促进了GC细胞的增殖和侵袭,而circ-CEP85L的过表达则使其逆转。此外,抑制circ-CEP85L促进体内肿瘤生长。从机械上讲,circ-CEP85L被确认为miR-942-5p的直接目标。此外,拯救实验表明,circ-CEP85L能够通过海绵miR-942-5p抑制GC细胞的增殖和侵袭。最后,western blot测定证实了miR-942-5p的下调有效地逆转了circ-CEP85L过表达诱导的NFKBIA的抑制作用。因此,我们得出结论,circ-CEP85L通过充当miR-942-5p海绵来促进NFKBIA表达; 因此,抑制GC增殖和侵袭。circ-CEP85L是GC医治的一个潜在靶点。

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