Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China.
Cancer Research Laboratory, Binzhou Medical University Hospital, Binzhou, China.
Cell Biol Int. 2021 Feb;45(2):368-381. doi: 10.1002/cbin.11493. Epub 2020 Oct 29.
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.
结直肠癌是一个重大的健康问题，对患者的生活质量有重大影响。5-氟尿嘧啶是用于这种类型癌症的最常见的化疗药物。虽然它的分子机制是通过抑制胸苷核苷酸合成酶来抑制 DNA 合成，但它的完整抗癌机制尚不清楚。膜相关环指蛋白 1（MARCH1）是一种 E3 泛素连接酶，在抗原呈递中发挥重要作用。然而，MARCH1 在结直肠癌中的研究尚未进行。在本研究中，我们证明 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 抑制 MARCH1 的表达，抑制结直肠肿瘤细胞的迁移和侵袭。Western blot 分析表明，MARCH1 通过调节上皮-间充质转化和 PI3K/AKT 通路。此外，5-氟尿嘧啶通过靶向 MARCH1 及其随后下调 PI3K/AKT 通路，抑制肿瘤细胞的增殖、迁移和侵袭，影响上皮-间充质转化的进展。总之，我们的研究表明，MARCH1 可能在结直肠癌中作为癌基因发挥作用，并且可能是 5-氟尿嘧啶的新靶分子。
