Department of Clinical Laboratory, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
J Biochem Mol Toxicol. 2024 Oct;38(10):e23831. doi: 10.1002/jbt.23831.
Helicobacter pylori (HP) is considered a major risk factor for gastric cancer (GC) and during this process, cytotoxin‑associated gene A (CagA) plays in essence. The study mainly focused on the molecular mechanism of circular RNA 0046854 (circ_0046854) in HP-induced GC. Clinically, 56 cases of GC and normal tissues were collected, and the GC tissues were divided into HP-negative GC tissues (HP) and 33 HP-positive GC tissues (HP). Tissue expression of circ_0046854, microRNA (miR)-511-3p and colony-stimulating factor 1 (CSF1) was tested. BGC-823/Cisplatin (DDP) resistant strain was induced and cell growth and DDP resistance were detected after HP infection. In vivo experiments were performed using a mouse xenograft model. The relationship between circ_0046854, miR-511-3p and CSF1 was confirmed. GC tissues especially HP cancer tissues expressed high circ_0046854 and CSF1 and low miR-511-3p. HP-induced circ_0046854 expression in GC cells through CagA. Inhibition of circ_0046854 or miR-511-3p elevation inhibited the growth and DDP resistance in GC cells. Circ_0046854 acted as a sponge for miR-511-3p, which targeted CSF1. Restoring CSF1 could abolish the inhibitory effect of miR-511-3p overexpression on CagA HP-induced GC progression in vitro. Circ_0046854 silencing repressed tumor growth and aggrandized the inhibiting effects of DDP on tumorigenesis in vivo. Circ_0046854/miR-511-3p/CSF1 axis may be involved in the development of HP-induced GC, thus providing new ideas for studying the mechanism of HP-related gastric diseases.
幽门螺杆菌（HP）被认为是胃癌（GC）的主要危险因素，在这一过程中，细胞毒素相关基因 A（CagA）起着本质作用。本研究主要聚焦于环状 RNA 0046854（circ_0046854）在 HP 诱导的 GC 中的分子机制。临床上，收集了 56 例 GC 和正常组织，将 GC 组织分为 HP 阴性 GC 组织（HP）和 33 例 HP 阳性 GC 组织（HP）。检测组织中 circ_0046854、微小 RNA（miR）-511-3p 和集落刺激因子 1（CSF1）的表达。诱导 BGC-823/顺铂（DDP）耐药株，HP 感染后检测细胞生长和 DDP 耐药性。采用小鼠异种移植模型进行体内实验。验证 circ_0046854、miR-511-3p 和 CSF1 之间的关系。GC 组织，特别是 HP 癌组织，表达高水平的 circ_0046854 和 CSF1，低水平的 miR-511-3p。HP 通过 CagA 诱导 GC 细胞中 circ_0046854 的表达。抑制 circ_0046854 或升高 miR-511-3p 可抑制 GC 细胞的生长和 DDP 耐药性。circ_0046854 作为 miR-511-3p 的海绵，靶向 CSF1。恢复 CSF1 可消除 miR-511-3p 过表达对体外 CagA HP 诱导 GC 进展的抑制作用。circ_0046854 沉默抑制肿瘤生长，增强 DDP 对体内肿瘤形成的抑制作用。Circ_0046854/miR-511-3p/CSF1 轴可能参与 HP 诱导的 GC 的发生发展，为研究 HP 相关胃疾病的机制提供了新思路。
