摘 要：结直肠癌的转移与肿瘤干细胞特性是导致患者预后不良的关键因素，但其分子调控机制尚未完全阐明。本研究发现，微小RNA miR-144-3p在结直肠癌细胞中显著低表达，而其潜在靶基因前列腺素内过氧化物合酶2（PTGS2）呈高表达，提示二者可能参与结直肠癌恶性进展的调控。双荧光素酶报告基因系统证实，miR-144-3p可直接靶向抑制PTGS2表达，进而在体外试验中显著抑制结直肠癌细胞的迁移、侵袭能力及肿瘤球形成效率，并同时下调干细胞标志物分化簇133（CD133）及核心转录因子Nanog同源框（Nanog）、SRY盒转录因子2（SOX2）、八聚体结合转录因子4（OCT4）的表达。体内裸鼠移植瘤模型进一步验证，过表达miR-144-3p可明显抑制肿瘤生长并降低PTGS2的表达水平。miR-144-3p通过负调控PTGS2/前列腺素E2（PGE2）信号通路，削弱肿瘤细胞的干性维持与上皮-间质转化（EMT）过程，从而发挥抑癌作用。本研究揭示了miR-144-3p-PTGS2轴在结直肠癌干细胞特性调控中的抑制效应，为靶向干预结直肠癌进展提供了新的理论依据与潜在治疗策略。
关键词：结直肠癌；裸鼠移植瘤；迁移；侵袭；细胞干性
中图分类号：R735.3+5 文献标志码：A DOI：10.3969/j.issn.1007-7146.2026.04.008
Abstract: Metastasis and tumor stem cell characteristics of colorectal cancer are key factors contributing to poor patient prognosis, yet their molecular regulatory mechanisms remain incompletely elucidated. This study found that miRNA miR-144-3p is significantly underexpressed in colorectal cancer cells, while its potential target gene prostaglandin-endoperoxide synthase 2 (PTGS2) is overexpressed, suggesting that both may be involved in the regulation of malignant progression in colorectal cancer. Using a dual-luciferase reporter gene system, it was confirmed that miR-144-3p can directly target and inhibit PTGS2 expression. In vitro experiments demonstrated that miR-144-3p significantly suppresses the migration and invasion capabilities of colorectal cancer cells, as well as tumor sphere formation efficiency. It also downregulates the expression of the stem cell marker cluster of differentiation 133 (CD133) and core transcription factors Nanog homeobox (Nanog), SRY-box transcription factor 2 (SOX2), and octamer binding transcription factor 4 (OCT4). In vivo, a nude mouse xenograft tumor model further validated that overexpression of miR-144-3p can markedly inhibit tumor growth and reduce PTGS2 expression level. Mechanistically, miR-144-3p weakens tumor cell stemness maintenance and the epithelial-mesenchymal transition (EMT) process by negatively regulating the PTGS2/prostaglandin E2 (PGE2) signaling pathway, thereby exerting an antitumor effect. This study is the first to reveal the inhibitory effect of the miR-144-3p-PTGS2 axis on the regulation of stemness characteristics in colorectal cancer, providing a new theoretical basis and potential therapeutic strategy for targeted intervention in colorectal cancer progression.
Keywords: colorectal cancer; nude mouse xenograft; migration; invasion; cell stemness
（Acta Laser Biology Sinica, 2026, 35(4): 352-360）
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