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VDR

SNAI1, ZEB1, E-cadherin (CDH1), and vitamin D receptor (VDR) genes regulate the epithelial-mesenchymal transition (EMT) that initiates the invasion process of many tumor cells. We hypothesized that this process could also affect the behavior of normal cells adjacent to the tumor. To verify this hypothesis, the expression level of these genes was determined by quantitative RT-PCR in tumor, normal adjacent, and normal distant tissues from 32 colorectal cancer (CC) patients. In addition, we extended the study to human HaCaT normal keratinocytes and SW480-ADH colon cancer cells co-cultured with SW480-ADH cells overexpressing the mouse Snai1 gene. Of 18 CC cases with SNAI1 expression in tumor tissue, five also had SNAI1 in normal adjacent tissue (NAT). expression of SNAI1 in tumor tissue correlated with downregulation of CDH1 and VDR genes in both tumor (P=0.047 and P=0.014, respectively) and NAT lacking SNAI1 expression (P=0.054 and P=0.003). ZEB1 expression was directly related to VDR expression in tumor tissue (r=0.39; P=0.027) and inversely to CDH1 in NAT (r=-0.46; P=0.010). CDH1 and VDR were also downregulated in SW480-ADH and MaCaT cells, respectively, when they were co-cultured with Snai1-expressing cells. Furthermore, cytokine analysis showed differences in the conditioned media obtained from the two cell types. These results indicate that histologically normal tissue adjacent to tumor tissue expressing the EMT-inducing gene SNAI1 shows alterations in the expression of epithelial differentiation genes such as CDH1 and VDR.

epithelial-mesenchymal transition(EMT) is the main reason for peritoneal fibrosis and the mechanism underlying peritoneal EMT were extensively studied in recent years. Recent researches showed that miRNAs were so important in the development of organ EMT and fibrosis, the role of microRNAs on peritoneal dialysis have also been studied. In the current study, we investigated microRNA-23(miR-23) expression in high glucose(HG) induced EMT in human mesotheial peritoneal cells(HPMCs). We found that HG promoted EMT, which was characterized by the upregulation of mesenchymal markers alpha-SMA and FN and downregulation of epithelial marker E-cadherin. The expression miR-23 showed a significant upregulation when treated with HG. Enhanced expression of miR-23 could aggravate HG induced EMT by targeting VDR, inhibition of miR-23 in HPMCs could reverse HG induced EMT by targeting VDR. Furthermore, VDRshRNA exacerbated the EMT process and reversed miR-23 inhibitor-attenuated EMT process in HPMCs. These data manifested that miR-23 played a key role in HG-induced EMT of HPMCs by targeting VDR.CI - Copyright (c) 2017 Elsevier Inc. All rights reserved.

Plasmacytoma variant translocation 1 (PVT1) is an lncRNA that plays vital roles in breast cancer (BC) pathogenesis. Increasing evidence suggests that miRNAs that reside in the PVT1 locus are the main driver of the oncogenic roles of PVT1 in cancer. However, the oncogenic role and underlying mechanism of miR-1204, located in the PVT1 locus, in human cancer is still unclear. In this study, we discovered that increased expression of miR-1204 is associated with poor prognosis in BC. Moreover, miR-1204 promotes proliferation, epithelial-mesenchymal transition and invasion of BC cells both in vitro and in vivo. Mechanistic investigations demonstrated that VDR is a novel target gene of miR-1204. Interference of VDR restored miR-1204-mediated BC cell proliferation, tumorigenesis, and metastasis. Collectively, our results demonstrated that the miR-1204-VDR pathway exerts oncogenic effects in BC with potential therapeutic applications in blocking BC development and progression.