Liu Chao, Zhou Xin, Wang Guangsheng, Zhu Chenyu, Xu Rui
Department of Gastrointestinal Surgery, Yichang Central People's Hospital, The First College of Clinical Medical Science, China Three Gorges University.
Tohoku J Exp Med. 2025 Jun 19;266(2):173-184. doi: 10.1620/tjem.2024.J145. Epub 2024 Dec 12.
Gastric cancer (GC) is one deadly malignancy globally. The potential clinical values of circular RNAs (circRNAs) in cancer diagnosis, prognosis, and treatment have been demonstrated in increasing studies. This research aimed at delving into the specific role of circRNA hsa_circ_0007376 (circMAP2K2) in GC development. CircMAP2K2, miR-556-5p, and CREB5 levels in GC cells and tissues were tested by RT-qPCR. Subcellular fractionation assay was employed for determining the distribution of circMAP2K2 in GC cell cytoplasm and nucleus. The binding potentials between circMAP2K2 (or CREB5) and miR-556-5p were confirmed through luciferase reporter assay. GC cell viability, growth, and metastasis were examined via CCK-8, colony formation, and Transwell assays. CREB5 protein level was assessed via western blot analysis. CircMAP2K2 was upregulated in GC cells and tissues vs. normal controls. CircMAP2K2 depletion hindered GC cell growth, migration, and invasion. Mechanically, circMAP2K2 elevated CREB5 level by completely binding with miR-556-5p. Overexpressing CREB5 abrogated the suppression of circMAP2K2 silencing on GC cell malignant behaviors. CircMAP2K2/miR-556-5p/CREB5 axis plays an oncogenic role in GC tumorigenesis.
胃癌(GC)是全球范围内一种致命的恶性肿瘤。越来越多的研究表明,环状RNA(circRNAs)在癌症诊断、预后和治疗中具有潜在的临床价值。本研究旨在深入探讨环状RNA hsa_circ_0007376(circMAP2K2)在胃癌发生发展中的具体作用。通过RT-qPCR检测胃癌细胞和组织中circMAP2K2、miR-556-5p和CREB5的水平。采用亚细胞分级分离试验确定circMAP2K2在胃癌细胞胞质和细胞核中的分布。通过荧光素酶报告基因试验证实circMAP2K2(或CREB5)与miR-556-5p之间的结合潜力。通过CCK-8、集落形成和Transwell试验检测胃癌细胞的活力、生长和转移情况。通过蛋白质免疫印迹分析评估CREB5蛋白水平。与正常对照相比,circMAP2K2在胃癌细胞和组织中上调。circMAP2K2的缺失阻碍了胃癌细胞的生长、迁移和侵袭。机制上,circMAP2K2通过与miR-556-5p完全结合提高了CREB5水平。过表达CREB5消除了circMAP2K2沉默对胃癌细胞恶性行为的抑制作用。circMAP2K2/miR-556-5p/CREB5轴在胃癌肿瘤发生中起致癌作用。