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)

WNT, FGF and Hedgehog signaling pathways network together during embryogenesis, tissue regeneration, and carcinogenesis. FGF16, FGF18, and FGF20 genes are targets of WNT-mediated TCF/LEF-beta-catenin-BCL9/BCL9L-PYGO transcriptional complex. SPROUTY (SPRY) and SPRED family genes encode inhibitors for receptor tyrosine kinase signaling cascades, such as those of FGF receptor family members and EGF receptor family members. Here, transcriptional regulation of SPRY1, SPRY2, SPRY3, SPRY4, SPRED1, SPRED2, and SPRED3 genes by WNT/beta-catenin signaling cascade was investigated by using bioinformatics and human intelligence (humint). Because double TCF/LEF-binding sites were identified within the 5'-promoter region of human SPRY4 gene, comparative genomics analyses on SPRY4 orthologs were further performed. SPRY4-FGF1 locus at human chromosome 5q31.3 and FGF2-NUDT6-SPATA5-SPRY1 locus at human chromosome 4q27-q28.1 were paralogous regions within the human genome. Chimpanzee SPRY4 gene was identified within NW_107083.1 genome sequence. Human, chimpanzee, rat and mouse SPRY4 orthologs, consisting of three exons, were well conserved. SPRY4 gene was identified as the evolutionarily conserved target of WNT/beta-catenin signaling pathway based on the conservation of double TCF/LEF-binding sites within 5'-promoter region of mammalian SPRY4 orthologs. Human SPRY4 mRNA was expressed in embryonic stem (ES) cells, brain, pancreatic islet, colon cancer, head and neck tumor, melanoma, and pancreatic cancer. WNT signaling activation in progenitor cells leads to the growth regulation of progenitor cells themselves through SPRY4 induction, and also to the growth stimulation of proliferating cells through FGF secretion. Epigenetic silencing and loss-of-function mutations of SPRY4 gene in progenitor cells could lead to carcinogenesis. SPRY4 is the pharmacogenomics target in the fields of oncology and regenerative medicine.
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PMID:FGF signaling inhibitor, SPRY4, is evolutionarily conserved target of WNT signaling pathway in progenitor cells. 1646 3

The epithelial-mesenchymal transition (EMT) is crucial for cancer progression. Evidence has shown that miR-22 and miR-214 play a key role in colon cancer progression; however, the underlying mechanism remains to be known. The effects of miR-22 and miR-214 on EMT are contradictory in different cancers, and whether miR-22 and miR-214 are involved in the colon cancer EMT process needs to be elucidated. In this study, we evaluated the exact role and the regulation mechanism of miR-22 and miR-214 in colon cancer. After transfection with miR-22 expression vector, the cell proliferation and migration capacity of HCT116 and RKO cells were significantly suppressed. Also, E-cadherin was increased and vimentin was decreased by miR-22 overexpression. Similar effects were also observed after miR-214 expression vector transfection. Dual-luciferase reporter confirmed that BCL9L is the target gene of both miR-22 and miR-214. Silencing of BCL9L inhibits cell proliferation and migration, and the expression of E-cadherin and vimentin was also altered by BCL9L knockdown, which was consistent with miR-22 or miR-214 transfection. Furthermore, miR-22 and miR-214 inhibited tumor growth in nude mice. Moreover, although the association between BCL9L's lower expression and longer survival time was statistically nonsignificant, a trend existed; further studies in a larger cohort are needed. Collectively, these data suggest that miR-22 and miR-214 inhibit cell proliferation, migration, and EMT of colon cancer, most likely by targeting BCL9L.-Sun, R., Liu, Z., Han, L., Yang, Y., Wu, F., Jiang, Q., Zhang, H., Ma, R., Miao, J., He, K., Wang, X., Zhou, D., Huang, C. miR-22 and miR-214 targeting BCL9L inhibit proliferation, metastasis, and epithelial-mesenchymal transition by down-regulating Wnt signliang in colon cancer.
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PMID:miR-22 and miR-214 targeting BCL9L inhibit proliferation, metastasis, and epithelial-mesenchymal transition by down-regulating Wnt signaling in colon cancer. 3069 96