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Authors Huang GL, Chen QX, Ma JJ, Sui SY, Wang YN, Shen DY
Received 3 January 2019
Accepted for publication 3 April 2019
Published 23 April 2019 Volume 2019:12 Pages 3087—3098
DOI https://doi.org/10.2147/OTT.S200261
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Ms Rachel Predeepa
Peer reviewer comments 2
Editor who approved publication: Dr XuYu Yang
Purpose: Retinoic
acid α (RARα) is overexpressed in various tumors and facilitates cancer
progression. Although RARα has been shown to facilitate colorectal cancer (CRC)
progression, more efforts to characterize mechanisms of RARα in CRC are needed
in order to develop better target-based drugs for tumor therapy.
Methods: RARα
expression in CRC was assessed by IHC. EdU, QPCR, Western blotting,
dual-luciferase reporter assay and ChIP were performed to explore the role of
RARα in CRC and the mechanism involoved.
Results: Here, we
show an overexpression of RARα in 73.5% (i.e., 25 of 34 human CRC specimens).
RARα knockdown decreased cell proliferation, migration, and invasion. Such
phenotypic manifestations can be correlated to lowered activation of Akt and
expression of PCNA (proliferating cell nuclear antigen) as well as MMP2 (matrix
metallopeptidase). Mechanistically, RARα facilitates CRC growth through Akt
signaling activation to cause levels of PCNA to be upregulated. Furthermore,
RARα promotes migration and invasion of CRC cells by directly recruiting
the MMP2 promoter
to enhance the expression of MMP2 .
Conclusions: These
findings demonstrate that CRC carcinogenesis is promoted by RARα via an
enhanced Akt signaling and by increasing MMP2 transcription.
CRC therapy can examine the use of RARα as a prospective molecular target.
Keywords: colorectal
cancer, RARα, proliferation, PCNA, MMP2