Abstract
BackgroundThe UHRF1 gene is an epigenetic modification factor that mediates tumor suppressor gene silencing in a variety of cancers. Related studies have reported that UHRF1 can inhibit the expression of the KISS1 gene. However, the regulatory mechanism underlying UHRF1 expression in colorectal cancer (CRC) is still unclear. The aim of this study was to gain a better understanding of the regulation of UHRF1 expression in CRC and to determine whether it regulates the mechanism by which KISS1 promotes CRC metastasis.MethodsIn the present study, the levels of miR-506, UHRF1 and KISS1 expression in CRC tissues and in human CRC cell lines were studied using quantitative real-time PCR (qRT-PCR) and Western blotting. Cell proliferation, migration, and invasion assays are used to detect cell proliferation, migration, and invasion. A dual-luciferase reporter system was used to confirm the target gene of miR-506.ResultsThis study found that UHRF1 protein is highly expressed in CRC tissues and negatively correlated with KISS1 protein expression. UHRF1 overexpression activates the PI3K/NF-κB signaling pathway by inhibiting the mRNA expression levels of pathway mediators. Bioinformatics analysis and luciferase reporter gene assays confirmed that miR-506 targets UHRF1.ConclusionThis study identified the regulation of UHRF1 expression in CRC and the mechanism of CRC metastasis. UHRF1 may be a new potential target molecule for future CRC metastasis treatment.
Highlights
Colorectal cancer (CRC) is a common malignant tumor of the digestive tract
In our investigations into the expression of UHRF1 in CRC, we found that UHRF1 was highly expressed in CRC according to The Cancer Genome Atlas (TCGA) database (p < 0.001; Figure 1A)
No significant difference in UHRF1 expression was found between T1 and T2 (p = 0.356); UHRF1 expression in T4 and T3 was significantly higher than that in T2 (p < 0.001; Figure 1B), but UHRF1 expression was significantly higher in T4 than in T3 (p < 0.001; Figure 1B)
Summary
Colorectal cancer (CRC) is a common malignant tumor of the digestive tract. The lack of typical clinical symptoms is one of the reasons for the low rate of early CRC diagnosis. Comprehensive treatments such as surgery, radiation therapy, chemotherapy, biological targeting, and immunotherapy are currently the standard treatment approaches for CRC (Ni et al, 2018; Ganesh et al, 2019; Li S. et al, 2019; Siravegna et al, 2019). The regulatory mechanism underlying UHRF1 expression in colorectal cancer (CRC) is still unclear. The aim of this study was to gain a better understanding of the regulation of UHRF1 expression in CRC and to determine whether it regulates the mechanism by which KISS1 promotes CRC metastasis
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