Zhao Yali, He Yan, Xiao Zhiyuan, Xin Le, Deng Mingjing, Yao Mingxia, Huang Guan
Department of Pathology, Shenzhen Longgang Central Hospital, Guangdong Province, Shenzhen, P. R. China.
Department of Pathology, Shenzhen People's Hospital, Guangdong Province, Shenzhen, P. R. China.
Mol Carcinog. 2025 Mar;64(3):450-462. doi: 10.1002/mc.23860. Epub 2024 Dec 2.
Colorectal cancer (CRC) is the most common gastrointestinal malignancy, with its recurrence and metastasis significantly affecting patient survival. Circular RNAs (circRNAs), a novel class of noncoding RNAs, have emerged as crucial contributors to CRC pathogenesis. However, the role of circEIF3I in CRC metastasis remains unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to assess circEIF3I, microRNA (miR)-328-3p, and NCAPH expression. CRC cell migration and invasion were determined via Transwell assays. Western blot analysis was utilized to define the protein expression of epithelial-mesenchymal transition (EMT) markers and NCAPH. Xenograft tumor was established for exploration into the function of circEIF3I in CRC metastasis to the liver and lung. The binding between miR-328-3p and circEIF3I or NCAPH was predicted through ENCORI or TargetScan platform and ascertained through dual-luciferase reporter assays. circEIF3I and NCAPH expression were found to be elevated in CRC tissues and cells, while miR-328-3p was downregulated. Functionally, circEIF3I knockdown inhibited CRC cell migration, invasion, EMT, and tumor metastasis. Mechanistic analyses revealed that circEIF3I can target miR-328-3p, while NCAPH was targeted by miR-328-3p. Furthermore, circEIF3I facilitated NCAPH expression in CRC cells by sequestering miR-328-3p. Notably, miR-328-3p inhibitor or NCAPH overexpression negated the effects of circEIF3I knockdown on preventing CRC progression in vitro. Taken together, circEIF3I elevated NCAPH expression by sponging miR-328-3p, thereby promoting CRC metastasis. These findings suggest that the circEIF3I/miR-328-3p/NCAPH axis represents a novel therapeutic target for CRC.
结直肠癌（CRC）是最常见的胃肠道恶性肿瘤，其复发和转移显著影响患者的生存率。环状RNA（circRNAs）是一类新型的非编码RNA，已成为CRC发病机制的关键因素。然而，circEIF3I在CRC转移中的作用仍不清楚。应用定量实时聚合酶链反应（qRT-PCR）来评估circEIF3I、微小RNA（miR）-328-3p和NCAPH的表达。通过Transwell实验测定CRC细胞的迁移和侵袭能力。利用蛋白质免疫印迹分析来确定上皮-间质转化（EMT）标志物和NCAPH的蛋白表达。建立异种移植瘤以探究circEIF3I在CRC向肝脏和肺转移中的作用。通过ENCORI或TargetScan平台预测miR-328-3p与circEIF3I或NCAPH之间的结合，并通过双荧光素酶报告基因实验进行验证。研究发现，circEIF3I和NCAPH在CRC组织和细胞中表达升高，而miR-328-3p表达下调。在功能上，circEIF3I敲低抑制了CRC细胞的迁移、侵袭、EMT和肿瘤转移。机制分析表明，circEIF3I可以靶向miR-328-3p，而NCAPH是miR-328-3p的靶标。此外，circEIF3I通过隔离miR-328-3p促进CRC细胞中NCAPH的表达。值得注意的是，miR-328-3p抑制剂或NCAPH过表达消除了circEIF3I敲低对体外预防CRC进展的影响。综上所述，circEIF3I通过吸附miR-328-3p提高NCAPH表达，从而促进CRC转移。这些发现表明，circEIF3I/miR-328-3p/NCAPH轴是CRC的一个新的治疗靶点。
