miRNA-4739 Targets URM1 to Inhibit JNK Signaling and Promote Apoptosis in Gastric Cancer
Основное содержимое статьи
Yaochu Zheng
Department of Gastroenterology, Yingtan People’s Hospital,Yingtan 335000, Jiangxi, China
ytsrmyyzyc@163.com
Yanyan Xiong
Department of Gastroenterology, Yingtan People’s Hospital,Yingtan 335000, Jiangxi, China
xiongyanyanzyc@163.com
Zhitai Zhu
Department of Gastroenterology, Yingtan People’s Hospital,Yingtan 335000, Jiangxi, China
zhuzhitai01@163.comАннотация
This study aimed to investigate the expression and clinical significance of miR-4739 and URM1 in gastric cancer (GC), clarifies their roles and molecular mechanisms in regulating GC cell proliferation, migration, invasion, apoptosis, and oxidative stress, and identifies potential biomarkers and therapeutic targets for GC. Fifty pairs of GC tissue and adjacent normal tissue samples were collected. qPCR was used to detect the expression of miR-4739 and URM1, and their correlations with clinicopathological parameters and TNM stage were analyzed. A dual-luciferase reporter assay verified the direct relationship between miR-4739 and URM1. The human GC cell line NCI-N87 was transfected with the miR-4739 mimic, pcDNA3-URM1, or negative control. CCK-8 and transwell assays were used to detect cell proliferation, migration, and invasion. Western blotting was used to detect URM1, p-JNK and Caspase-3. Co-immunoprecipitation (Co-IP) confirmed the interaction between URM1 and JNK. The levels of intracellular reactive oxygen species (ROS) and protein disulfide bonds were measured to evaluate oxidative stress. The JNK inhibitor SP600125 was used for rescue experiments. miR-4739 was significantly down regulated, and URM1 was upregulated in GC tissues, and its expression levels were closely correlated with TNM stage (T3/T4) and tumor invasion depth (p<0.01). miR-4739 directly targets and negatively regulates URM1. Over expression of miR-4739 inhibited the proliferation, migration, and invasion of NCI-N87 cells; promoted apoptosis; reduced the expression of URM1 and p-JNK, increased Caspase-3 level, and alleviated oxidative stress. Over expression of URM1 reversed the effects of miR-4739. Co-immunoprecipitation confirmed a direct interaction between URM1 and JNK. Inhibition of JNK signaling blocks URM1-mediated oxidative stress and malignant biological behavior. miR-4739 is expressed at low levels in GC and serves as a tumor suppressor. By targeting URM1, miR-4739 inhibits JNK signaling pathway activation, reduces oxidative stress, promotes apoptosis, and ultimately suppresses the malignant progression of GC. Thus, the miR-4739/URM1/JNK axis may be a potential diagnostic biomarker and therapeutic target for GC.
Информация о статье
##plugins.generic.dates.accepted## 2026-06-06
##plugins.generic.dates.published## 2026-06-27
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