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Hsa_circ_0013729 通过以ceRNA和RBP依赖的方式调控MEF2D促进胃癌进展。

Hsa_circ_0013729 Promotes Gastric Cancer Progression by Regulating MEF2D in ceRNA- and RBP- Dependent Manners.

作者信息

Li Huazhi, Chen Shaofei, Zhong Yangqing, Meng Lingjia

机构信息

General Surgery Department, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China.

出版信息

Biochem Genet. 2025 Aug 6. doi: 10.1007/s10528-025-11216-x.

DOI:10.1007/s10528-025-11216-x
PMID:40767994
Abstract

Circular RNAs (circRNAs) are emerging as major regulatory factors in gastric cancer progression. Here, in addition to the regulatory role of hsa_circ_0013729, we also evaluated its biomarker potential in gastric cancer. RNA-Seq profiles were obtained from GSE194384 and GSE184882. 116 gastric cancer specimens and adjacent para- tumor gastric tissues were analyzed for the expression of hsa_circ_0013729. The functional (proliferative, migratory, and invasive) significance of hsa_circ_0013729 was evaluated by cell experiments. The competing theories of endogenous RNAs and RNA-binding proteins were used to explore the underlying mechanism. Analyses of GSE194384 and GSE184882 identified hsa_circ_0013729 as a dysregulated circRNA in gastric cancer. The quantification of hsa_circ_0013729 in our patient cohort revealed its upregulation, diagnostic significance (ROC-AUC = 0.94, 95% confidence interval: 0.9149 to 0.9718; p < 0.0001), and prognostic value with a hazard ratio of 2.65 in gastric cancer. Hsa_circ_0013729 was identified as a potential driver in gastric cancer cell proliferation, migration, and invasion. Hsa_circ_0013729 acted as a ceRNA for miR-361-3p and interfered with the binding between miR-361-3p and MEF2D. Hsa_circ_0013729 interacted with HNRNPIL1 to stabilize MEF2D mRNA.Hsa_circ_0013729 may promote gastric cancer via the miR-361-3p/MEF2D axis and HNRNPUL1/MEF2D axis, showing potential as a biomarker and therapeutic target.

摘要

环状RNA(circRNAs)正在成为胃癌进展中的主要调节因子。在此,除了hsa_circ_0013729的调节作用外,我们还评估了其在胃癌中的生物标志物潜力。从GSE194384和GSE184882获取RNA测序图谱。对116例胃癌标本及相邻癌旁胃组织进行hsa_circ_0013729表达分析。通过细胞实验评估hsa_circ_0013729的功能(增殖、迁移和侵袭)意义。利用内源性RNA和RNA结合蛋白的竞争理论来探究潜在机制。对GSE194384和GSE184882的分析确定hsa_circ_0013729为胃癌中失调的环状RNA。在我们的患者队列中对hsa_circ_0013729进行定量分析,结果显示其上调、具有诊断意义(ROC-AUC = 0.94,95%置信区间:0.9149至0.9718;p < 0.0001),以及在胃癌中的预后价值,风险比为2.65。Hsa_circ_0013729被确定为胃癌细胞增殖、迁移和侵袭的潜在驱动因素。Hsa_circ_0013729作为miR-361-3p的竞争性内源RNA,干扰miR-361-3p与MEF2D之间的结合。Hsa_circ_0013729与HNRNPIL1相互作用以稳定MEF2D mRNA。Hsa_circ_0013729可能通过miR-361-3p/MEF2D轴和HNRNPUL1/MEF2D轴促进胃癌,显示出作为生物标志物和治疗靶点的潜力。

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