Open AccessThe overexpression of AUF1 in colorectal cancer predicts a poor prognosis and promotes cancer progression by activating ERK and AKT pathways
Author(s) -
Tian XinYuan,
Li Jin,
Liu TengHui,
Li DanNi,
Wang JingJing,
Zhang He,
Deng ZhouLu,
Chen FuJun,
Cai JianPing
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.3464
Subject(s) - gene knockdown , cancer research , protein kinase b , mapk/erk pathway , cell growth , carcinogenesis , biology , colorectal cancer , metastasis , cell migration , downregulation and upregulation , pi3k/akt/mtor pathway , immunohistochemistry , signal transduction , cancer , cell culture , cell , microbiology and biotechnology , immunology , gene , biochemistry , genetics
Background AUF1 is one of the AU‐rich binding proteins, which promotes rapid ARE‐mRNA degradation. Recently, it has been reported that AUF1 is involved in regulating the antioxidant system because of its capacity to bind specifically to RNA containing oxidized bases and degrade oxidized RNA. Many antioxidant proteins have been reported to be overexpressed in colorectal cancer (CRC), however, the role of AUF1 in the progression of CRC has not been explored. Methods The expression level of AUF1 protein in human CRC cell lines and CRC tissues was detected by western blotting and immunohistochemistry (IHC. The effects of AUF1 knockdown on CRC cell proliferation, migration, invasion and changes in the signaling pathways were evaluated using a cell counting kit‐8 (CCK‐8), Transwell assays and western blotting. Subcutaneous xenograft tumor model was employed to further substantiate the role of AUF1 in CRC. Results AUF1 protein was upregulated in CRC tissues and CRC cells, and high expression of AUF1 was significantly associated with advanced AJCC stage ( P = .001), lymph node metastasis ( P = .007), distant metastasis ( P = .038) and differentiation ( P = .009) of CRC specimens. CRC patients with the high expression of AUF1 had an extremely poor prognosis. The knockdown of AUF1 suppressed CRC cell line proliferation, migration and invasion, inhibited CRC cells tumorigenesis and growth in nude mice, and reduced phosphorylated‐ERK1/2 and phosphorylated AKT in CRC cells. Conclusion Our findings demonstrate that AUF1 is probably involved in the progression of CRC via the activation of the ERK1/2 and AKT pathways. AU‐rich RNA‐binding factor 1 could be used as a novel prognostic biomarker and a potential therapeutic target for CRC.