Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellular hallmark of kidney repair is a rapid proliferation of renal tubular epithelial cells ultimately leading to the restoration of nephron structure and function. Netrin-1 was discovered as a neural guidance cue and found to be expressed outside the nervous system, including in kidney. Previous work showed that netrin-1 is upregulated in response to ischemic injury and ameliorates ischemic injury. The objectives of this study were to determine the role of netrin-1 in renal tubular epithelial cell proliferation and migration in vitro. Real-time RT-PCR analysis showed that netrin-1 and its receptors UNC5B and neogenin are highly expressed in cultured mouse renal epithelial cells (TKPTS), whereas the expression of the Deleted in Colon Cancer (DCC), UNC5A, UNC5C, and UNC5D receptors is negligible or undetectable. Netrin-1 protein was induced in the edges of mechanical wounds in vitro. Netrin-1 increased TKPTS cell proliferation in a dose-dependent manner. The netrin-1-induced increase in TKPTS cell proliferation was completely prevented by small interfering RNA (siRNA) inhibition of UNC5B receptor but not UNC5C receptor expression. Netrin-1 also increased TKPTS cell migration in vitro, and this was also mediated through the UNC5B receptor. Netrin-1 increased the phosphorylation of Akt and ERK. Inhibition of phosphatidylinositol 3-kinase and MEK1/2 completely inhibited netrin-1-induced cell proliferation but not migration. These results indicate that netrin-1 increases renal tubular epithelial cell proliferation and migration through the UNC5B receptor. Moreover, the increase in cell proliferation, but not migration, was mediated via activation of Akt and ERK pathways.
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PMID:Netrin-1 increases proliferation and migration of renal proximal tubular epithelial cells via the UNC5B receptor. 1921 85

Background: Colon cancer is the most frequently lethal cancer in digestive system. Herein, we tested the influences of UNC5B antisense lncRNA 1 (UNC5B-AS1) on colon cancer cell growth and metastasis, along with the regulatory function of UNC5B-AS1 in microRNA-622 (miR-622) expression.Methods: Firstly, UNC5B-AS1 expression in colon cancer tissues and corresponding normal tissues were tested. Then, the influences of silencing UNC5B-AS1 by sh-UNC5B-AS1 transfection on colon cancer HCT116 and Caco-2 cell viability, proliferation, migration, invasion and apoptosis, as well as miR-622 expression were assessed, respectively. Subsequently, whether miR-622 attended to the influences of silencing UNC5B-AS1 on HCT116 and Caco-2 cells were probed. Finally, the activities of AMPK and PI3K/AKT pathways in cells were analysed.Results: UNC5B-AS1 had high expression level in colon cancer tissues. Silencing UNC5B-AS1 repressed HCT116 and Caco-2 cell proliferation, migration and invasion, but boosted cell apoptosis. Moreover, silencing UNC5B-AS1 raised miR-622 expression in HCT116 and Caco-2 cells. miR-622 inhibitor transfection weakened the influences of silencing UNC5B-AS1 on HCT116 and Caco-2 cells. Besides, Silencing UNC5B-AS1 suppressed AMPK and PI3K/AKT pathways via raising miR-622.Conclusion: Silencing UNC5B-AS1 repressed colon cancer growth and metastasis might be through raising miR-622 expression and suppressing AMPK and PI3K/AKT pathways.
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PMID:Silencing UNC5B antisense lncRNA 1 represses growth and metastasis of human Colon cancer cells via raising miR-622. 3185 93

While it is now accepted that nutrition can influence the epigenetic modifications occurring in colorectal cancer (CRC), the underlying mechanisms are not fully understood. Among the tumor suppressor genes frequently epigenetically downregulated in CRC, the four related genes of the UNC5 family: UNC5A, UNC5B, UNC5C and UNC5D encode dependence receptors that regulate the apoptosis/survival balance. Herein, in a mouse model of CRC, we found that the expression of UNC5A, UNC5B and UNC5C was diminished in tumors but only in mice subjected to a High Carbohydrate Diet (HCD) thus linking nutrition to their repression in CRC. O-GlcNAcylation is a nutritional sensor which has enhanced levels in CRC and regulates many cellular processes amongst epigenetics. We then investigated the putative involvement of O-GlcNAcylation in the epigenetic downregulation of the UNC5 family members. By a combination of pharmacological inhibition and RNA interference approaches coupled to RT-qPCR (Reverse Transcription-quantitative Polymerase Chain Reaction) analyses, promoter luciferase assay and CUT&RUN (Cleavage Under Target & Release Using Nuclease) experiments, we demonstrated that the O-GlcNAcylated form of the histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2) represses the transcription of UNC5A in human colon cancer cells. Collectively, our data support the hypothesis that O-GlcNAcylation could represent one link between nutrition and epigenetic downregulation of key tumor suppressor genes governing colon carcinogenesis including UNC5A.
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PMID:O-GlcNAcylation Links Nutrition to the Epigenetic Downregulation of UNC5A during Colon Carcinogenesis. 3312 52