Department of Gastrointestinal Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China.
Cell Cycle. 2022 May;21(10):1091-1102. doi: 10.1080/15384101.2022.2041354. Epub 2022 Feb 28.
Gastric cancer (GC) is one of the most common malignant tumors. Circular RNA (circRNA) has been shown to be involved in the progression of GC. However, the function of circ_0008035 in GC has not been studied. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_0008035, microRNA-1256 (miR-1256) and carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, and transwell assay were used to detect cell function. Western blot examined the protein levels of Ki67, Bax, MMP-2, and CEACAM6. The relationship between miR-1256 and circ_0008035 or CEACAM6 was verified by dual-luciferase reporter assays and RNA pull down. The xenotransplantation model was established in BALB/c nude mice to study the role of circ_0008035 in vivo. Circ_0008035 and CEACAM6 were significantly high-expressed in GC tissues and cells. Silencing of circ_0008035 reduced GC cell proliferation, migration, and invasion while enhancing apoptosis. MiR-1256 was a target of circ_0008035. The inhibition effect of circ_0008035 knockdown on the malignant behavior of GC cells could be reversed by miR-1256 inhibitor. In addition, CEACAM6 was a target of miR-1256. Overexpression of CEACAM6 partially restored the inhibitory effect of miR-1256 on cell progression. Animal experiments confirmed the anti-tumor effect of circ_0008035 knockdown in vivo. Collectively, circ_0008035 regulated the expression of CEACAM6 by sponging miR-1256, thereby promoting the development of GC. Our data provided a novel targeted therapy for GC.
胃癌（GC）是最常见的恶性肿瘤之一。环状 RNA（circRNA）已被证明参与了 GC 的进展。然而，circ_0008035 在 GC 中的功能尚未研究。实时定量聚合酶链反应（qRT-PCR）用于检测 circ_0008035、微小 RNA-1256（miR-1256）和癌胚抗原相关细胞粘附分子 6（CEACAM6）的表达。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）检测细胞功能，5-乙炔基-2'-脱氧尿苷（EdU）检测，流式细胞术和 Transwell 检测。Western blot 检测 Ki67、Bax、MMP-2 和 CEACAM6 的蛋白水平。通过双荧光素酶报告基因检测和 RNA 下拉实验验证了 miR-1256 与 circ_0008035 或 CEACAM6 的关系。在 BALB/c 裸鼠中建立异种移植模型，研究 circ_0008035 在体内的作用。circ_0008035 和 CEACAM6 在 GC 组织和细胞中高表达。circ_0008035 沉默可降低 GC 细胞增殖、迁移和侵袭，促进细胞凋亡。miR-1256 是 circ_0008035 的靶基因。circ_0008035 敲低对 GC 细胞恶性行为的抑制作用可被 miR-1256 抑制剂逆转。此外，CEACAM6 是 miR-1256 的靶基因。CEACAM6 的过表达部分恢复了 miR-1256 对细胞进展的抑制作用。动物实验证实了 circ_0008035 敲低在体内的抗肿瘤作用。综上所述，circ_0008035 通过海绵吸附 miR-1256 调节 CEACAM6 的表达，从而促进 GC 的发展。我们的数据为 GC 提供了一种新的靶向治疗方法。
