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5‐FU inhibits migration and invasion of CRC cells through PI3K/AKT pathway regulated by MARCH1
Author(s) -
Wang Nuan,
Yang Lijuan,
Dai Juanjuan,
Wu Yan,
Zhang Ranran,
Jia Xingfang,
Liu Chengxia
Publication year - 2021
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11493
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , cancer research , oncogene , colorectal cancer , ubiquitin ligase , epithelial–mesenchymal transition , chemistry , transfection , downregulation and upregulation , biology , ubiquitin , cancer , cell culture , cell cycle , microbiology and biotechnology , cell , signal transduction , biochemistry , gene , genetics
Abstract 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.