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Authors Hong M, Zhang Z, Chen Q, Lu Y, Zhang J, Lin C, Zhang F, Zhang W, Li X, Zhang W, Li X
Received 3 September 2018
Accepted for publication 16 November 2018
Published 31 December 2018 Volume 2019:11 Pages 369—378
DOI https://doi.org/10.2147/CMAR.S186236
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 2
Editor who approved publication: Dr Rituraj Purohit
Background: Interferon
regulatory factor 1 (IRF1) plays a role in the immune response, cellular
necrosis, DNA damage, and DNA repair, offering an attractive target for
anticancer treatment. However, little is known about the role of IRF1 in the
regulation of CRC progression.
Methods: Quantitative
reverse transcription-PCR, Western blot, and immunohistochemistry were used to
examine the expression level of IRF1; Cell Counting Kit-8, migration assay, and
xenograft mouse models were used to examine the function of IRF1 in CRC cell
lines; a ChIP assay was used to examine the binding between IRF1 and Ras
association domain-containing protein 5 (RASSF5).
Results: IRF1
expression was lower in colorectal cancer (CRC) than in normal mucosa and the
IRF1 expression level was inversely associated with CRC metastasis. In
addition, IRF1 could inhibit CRC cell proliferation, migration, and metastasis
in vivo and in vitro; IRF1 also induced cell cycle arrest but had no effect on
cell apoptosis. IRF1 enhanced the expression of RASSF5 by increasing its
promoter activity. Moreover, this study revealed a novel mechanism for
inhibiting the RAS-RAC1 pathway by overexpression of RASSF5.
Conclusion: Altogether,
the results indicate that IRF1, which promotes RASSF5 expression, suppresses
CRC metastasis and proliferation possibly through downregulation of the
RAS-RAC1 pathway.
Keywords: IRF1,
RASSF5, Rac1, Ras, colorectal cancer