Department of Pathology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China.
Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China.
Histol Histopathol. 2023 Aug;38(8):893-905. doi: 10.14670/HH-18-538. Epub 2022 Oct 24.
Gallbladder carcinoma (GBC) is a common cancer disease with high mortality. Circular RNA_0008234 (circ_0008234) has been shown to play a key role in many tumors, including GBC. However, the function between circ_0008234 and microRNA-204-5p (miR-204-5p) in the progression of GBC has not been clarified.
Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expressions of circ_0008234, miR-204-5p and fibroblast growth factor receptor-2 (FGFR2) in GBC cells and tissues. Western blot was used to detect the expression of relative proteins. Cell proliferation, apoptosis, invasion and migration were detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, thymidine analog 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, transwell assay and wound healing assay. Mechanically, the interaction of miR-204-5p with circ_0008234/FGFR2 was notarized by dual-luciferase reporter assay. A xenotransplantation model was established to study the role of circ_0008234 in vivo.
Circ_0008234 and FGFR2 were highly expressed in GBC tissues and cells. Silencing circ_0008234 down-regulated cell proliferation, migration and invasion of NOZ and SGC-996 cells, while miR-204-5p inhibitors reversed these effects. In addition, overexpression of FGFR2 restored the cell malignant behavior of GBC cells inhibited by miR-204-5p mimic. Animal experiments confirmed the anti-tumor effect of silenced circ_0008234 in vivo.
Circ_0008234 mediated GBC via the miR-204-5p/FGFR2 axis, providing a novel targeted therapy for gallbladder carcinoma.
胆囊癌（GBC）是一种死亡率较高的常见癌症疾病。环状 RNA_0008234（circ_0008234）已被证明在许多肿瘤中发挥关键作用，包括 GBC。然而，circ_0008234 与 microRNA-204-5p（miR-204-5p）在 GBC 进展中的功能尚未阐明。
使用实时定量聚合酶链反应（qRT-PCR）检测 GBC 细胞和组织中 circ_0008234、miR-204-5p 和成纤维细胞生长因子受体 2（FGFR2）的表达。使用 Western blot 检测相对蛋白的表达。通过 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）测定、胸苷类似物 5-乙炔基-2'-脱氧尿苷（EdU）测定、流式细胞术、Transwell 测定和划痕愈合测定检测细胞增殖、凋亡、侵袭和迁移。通过双荧光素酶报告基因测定证实 miR-204-5p 与 circ_0008234/FGFR2 的相互作用。建立异种移植模型研究 circ_0008234 在体内的作用。
circ_0008234 和 FGFR2 在 GBC 组织和细胞中高表达。沉默 circ_0008234 下调了 NOZ 和 SGC-996 细胞的增殖、迁移和侵袭，而 miR-204-5p 抑制剂则逆转了这些作用。此外，过表达 FGFR2 恢复了 miR-204-5p 模拟物抑制的 GBC 细胞的恶性行为。动物实验证实了沉默 circ_0008234 在体内的抗肿瘤作用。
circ_0008234 通过 miR-204-5p/FGFR2 轴介导 GBC，为胆囊癌提供了一种新的靶向治疗方法。
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