Colorectal cancer is a major health problem with a significant impact on the patients' quality of life. 5‐Fluorouracil is the most common chemotherapy drug used for this type of cancer. While its molecular mechanism is the inhibition of DNA synthesis via the inhibition of thymine nucleotide synthetase, its complete anticancer mechanism is not clear. Membrane‐associated RING‐CH‐1 (MARCH1) is an E3 ubiquitin ligase that plays an important role in antigen presentation. However, MARCH1 has not been studied in the context of colorectal cancer. In this study, we demonstrated that MARCH1 is highly expressed in colorectal cancer tissues and cell lines. Furthermore, migration and invasion of colorectal tumor cells were inhibited via transfection with small interfering RNAs to suppress the expression of MARCH1. The western blot analysis showed that MARCH1 regulates epithelial–mesenchymal transition and the PI3K/AKT pathway. Moreover, 5‐fluorouracil inhibited the proliferation, migration, and invasion of tumor cells, via the targeting of MARCH1 and the consequent downregulation of the PI3K/AKT pathway, impacting the progression of epithelial–mesenchymal transition. In conclusion, our study shows that MARCH1 may play a role as an oncogene in colorectal cancer and may represent a new target molecule of 5‐fluorouracil.

中文翻译：

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5-FU 通过 MARCH1 调控的 PI3K/AKT 通路抑制 CRC 细胞的迁移和侵袭

结直肠癌是一个严重的健康问题，对患者的生活质量产生重大影响。5-氟尿嘧啶是治疗此类癌症最常用的化疗药物。虽然其分子机制是通过抑制胸腺嘧啶核苷酸合成酶来抑制DNA合成，但其完整的抗癌机制尚不清楚。膜相关 RING-CH-1 (MARCH1) 是一种 E3 泛素连接酶，在抗原呈递中起重要作用。然而，尚未在结直肠癌的背景下研究 MARCH1。在这项研究中，我们证明了 MARCH1 在结直肠癌组织和细胞系中高度表达。此外，通过转染小干扰RNA来抑制MARCH1的表达，可以抑制结直肠肿瘤细胞的迁移和侵袭。蛋白质印迹分析显示 MARCH1 调节上皮间质转化和 PI3K/AKT 通路。此外，5-氟尿嘧啶通过靶向 MARCH1 和随后下调 PI3K/AKT 通路抑制肿瘤细胞的增殖、迁移和侵袭，影响上皮-间质转化的进程。总之，我们的研究表明 MARCH1 可能在结直肠癌中发挥致癌基因的作用，并且可能代表 5-氟尿嘧啶的新靶分子。