Department of Digestive Medicine, Henan Provincial People's Hospital, Zhengzhou, China.
Department of Pharmaceutical Laboratory, Henan Vocational College of Nursing, Anyang, China.
Bioengineered. 2021 Dec;12(2):9739-9752. doi: 10.1080/21655979.2021.1989259.
The competing endogenous RNA (ceRNA) activity of circular RNAs (circRNAs) has been implicated in the development of gastric cancer. Here, we sought to explore the ceRNA function of circRNA Jupiter microtubule associated homolog 1 (circ_HN1) in gastric tumorigenesis. Circ_HN1, microRNA (miR)-628-5p, and NT5E expression levels were quantified by qRT-PCR and western blot. Dual-luciferase reporter assays were used to assess the direct relationship between miR-628-5p and circ_HN1 or NT5E. Our data showed that circ_HN1 expression was enhanced in human gastric cancer. Depletion of circ_HN1 impeded cell proliferation, spheroid formation, invasion, and migration and promoted apoptosis , as well as diminished tumor growth . NT5E was a downstream effector of circ_HN1 function. NT5E was targeted and inhibited by miR-628-5p through the perfect complementary site in NT5E 3'UTR, and circ_HN1 affected NT5E expression through miR-628-5p competition. Moreover, depletion of miR-628-5p reversed the effects of circ_HN1 silencing on regulating cell functional behaviors. Our findings identify a novel ceRNA network, the circ_HN1/miR-628-5p/NT5E axis, for the oncogenic activity of circ_HN1 in gastric cancer, highlighting circ_HN1 inhibition as a promising targeted treatment against gastric cancer.
环状 RNA（circRNA）的竞争内源性 RNA（ceRNA）活性被认为与胃癌的发展有关。在这里，我们试图探讨 circRNA 木星微管相关同源物 1（circ_HN1）在胃肿瘤发生中的 ceRNA 功能。通过 qRT-PCR 和 Western blot 定量检测 circ_HN1、microRNA（miR）-628-5p 和 NT5E 的表达水平。双荧光素酶报告基因实验用于评估 miR-628-5p 与 circ_HN1 或 NT5E 之间的直接关系。我们的数据表明，circ_HN1 在人胃癌中表达增强。circ_HN1 的耗竭抑制了细胞增殖、球体形成、侵袭和迁移，并促进了细胞凋亡，同时减少了肿瘤生长。NT5E 是 circ_HN1 功能的下游效应物。NT5E 是 circ_HN1 通过 NT5E 3'UTR 中完美互补位点的作用靶点，并通过 miR-628-5p 竞争抑制 NT5E 的表达。此外，miR-628-5p 的耗竭逆转了 circ_HN1 沉默对调节细胞功能行为的影响。我们的研究结果确定了一个新的 ceRNA 网络，circ_HN1/miR-628-5p/NT5E 轴，用于 circ_HN1 在胃癌中的致癌活性，突出了抑制 circ_HN1 作为一种有前途的针对胃癌的靶向治疗方法。
