Zhai Xiang-Ming, Yang Yi-Qi, Lin Li, Luo Huan-Chang, Guo Zhi-Wei, Wu Ying-Song
Institute of Antibody Engineering, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China.
Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
BMC Cancer. 2025 Aug 13;25(1):1313. doi: 10.1186/s12885-025-14688-7.
Gastric cancer (GC) is the fourth most common cause of cancer death and has the fifth highest incidence of cancer worldwide. Circular RNAs (circRNAs) have emerged as essential regulators of tumorigenesis and cancer progression. However, the underlying regulatory mechanisms and their roles as diagnostic biomarkers have yet to be well elucidated in GC.
In this study, we implemented genome-wide sequencing to identify circRNAs whose expression in plasma extracellular vesicles (EVs) significantly changed. Functional experiments were performed to assess its effect on the proliferation, viability, migration and apoptosis of GC cell lines. Luciferase reporter and RNA pull-down assays were used to validate their combinations. Finally, RNA-Seq and RT-qPCR were used to identify the downstream regulatory pathway involved.
We found that the circRNA of MORC family CW-type zinc finger 1 gene (circMORC1) was decreased in the plasma EVs of GC patients but increase in GC cells. In vivo, circMORC1 promoted proliferation, viability, and migration and inhibited apoptosis in AGS and SGC-7901 GC cell lines. CircMORC1 was found to bind to miR-103a-1-5p, which is essential for the regulation of phenotypes. In addition, the Wnt pathway was found to be the downstream regulatory pathway of circMORC1 through a miR-103a-1-5p sponge.
Our results shed light on circMORC1 promotes the proliferation of gastric cancer cells, as a RNA sponge of miR-103a-1-5p and counteracted the down-regulation of Wnt signaling function of miR-103a-1-5p. Revealed a novel mechanism by which circMORC1 regulates tumorigenesis in gastric cancer and provided a new biomarker for GC diagnosis and prognosis.
胃癌（GC）是癌症死亡的第四大常见原因，在全球癌症发病率中排名第五。环状RNA（circRNAs）已成为肿瘤发生和癌症进展的重要调节因子。然而，其潜在的调控机制及其作为诊断生物标志物的作用在胃癌中尚未得到充分阐明。
在本研究中，我们进行了全基因组测序，以鉴定血浆细胞外囊泡（EVs）中表达显著变化的circRNAs。进行功能实验以评估其对GC细胞系增殖、活力、迁移和凋亡的影响。使用荧光素酶报告基因和RNA下拉实验来验证它们的组合。最后，使用RNA测序和逆转录定量聚合酶链反应（RT-qPCR）来鉴定所涉及的下游调控途径。
我们发现MORC家族CW型锌指蛋白1基因（circMORC1）的circRNA在GC患者的血浆EVs中减少，但在GC细胞中增加。在体内，circMORC1促进AGS和SGC-7901 GC细胞系的增殖、活力和迁移，并抑制其凋亡。发现circMORC1与miR-103a-1-5p结合，这对表型的调节至关重要。此外，通过miR-103a-1-5p海绵发现Wnt通路是circMORC1的下游调控通路。
我们的结果揭示了circMORC1作为miR-103a-1-5p的RNA海绵促进胃癌细胞增殖，并抵消了miR-103a-1-5p对Wnt信号功能的下调作用。揭示了circMORC1调节胃癌肿瘤发生的新机制，并为GC诊断和预后提供了新的生物标志物。
