LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

DR4 mediates the progression, invasion, metastasis and survival of colorectal cancer through the Sp1/NF1 switch axis on genomic locus

Photo from wikipedia

The single nucleotide polymorphism (SNP), −397G > T (rs13278062) polymorphism, in the promoter of Death Receptor 4 (DR4) had been reported to be associated with a significantly increased risk for bladder cancer.… Click to show full abstract

The single nucleotide polymorphism (SNP), −397G > T (rs13278062) polymorphism, in the promoter of Death Receptor 4 (DR4) had been reported to be associated with a significantly increased risk for bladder cancer. However, the association of this SNP with the risk of colorectal cancer has not been reported. In this study, we performed a case–control study in 1,078 colorectal cancer patients and 1,175 matched healthy controls to evaluate the association of the potential functional genetic variants in DR4 with risk and survival of colorectal cancer. PCR‐TaqMan were used to genotype the rs13278062, rs1000294 and rs2235126 polymorphisms. We found that subjects carrying the rs13278062 GT/TT genotypes had a significantly lower risk and increased survival time when compared to the GG genotype. We also constructed the rs13278062 GT/TT genotype in SW480 and SW620 cells (rs13278062 is GG in both cell lines) with the CRISPR/Cas9 system. Flow cytometry experiments showed that the rs13278062 TT genotype promoted apoptosis in colorectal cancer cells. In vitro and in vivo experiments established that the rs13278062 G to T mutation inhibited carcinogenesis and metastasis of colorectal cancer. Chromatin immunoprecipitation (ChIP) assays revealed that the rs13278062 G > T polymorphism altered the binding affinity of the transcription factors Sp1/NF1 to the rs13278062 mutation region. Immunohistochemistry, western blot, and qPCR corroborated that the rs13278062 GT/TT genotypes increased the expression of DR4 protein in colorectal cancer tissues and cells. In conclusion, these findings indicate that DR4 mediated progression, invasion, metastasis and survival of colorectal cancer via the Sp1/NF1 switch axis on genomics locus.

Keywords: dr4; colorectal cancer; metastasis; cancer; survival colorectal; sp1 nf1

Journal Title: International Journal of Cancer
Year Published: 2018

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.