IRF6 Is Involved in the Regulation of Cell Proliferation and Transformation in MCF10A Cells Downstream of Notch Signaling

Zengin, Talip; Ekinci, Burcu; Küçükköse, Cansu; Yalcin-Ozuysal, Özden

doi:10.1371/journal.pone.0132757

Cited by 19 publications

(17 citation statements)

References 38 publications

(75 reference statements)

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“…In addition, previous studies showed that IRF6 is a downstream target gene of the NOTCH signaling pathway and induced by the NOTCH signaling pathway in breast cancer and keratinocytes (9, 31, 32). NOTCH signaling pathway has been reported to play critical roles in the development and progression of human cancers through regulating ZEB1 expression and EMT pathway (33–38).…”

Section: Discussionmentioning

confidence: 98%

IRF6 Is Directly Regulated by ZEB1 and ELF3, and Predicts a Favorable Prognosis in Gastric Cancer

Cheng

Wang

et al. 2019

Front. Oncol.

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Interferon regulatory factor 6 (IRF6) acts as a tumor suppressor and controls cell differentiation in ectodermal and craniofacial tissues by regulating expression of target genes. However, its function in gastric cancer (GC) remains unknown to date. In this study, we found that the IRF6 expression was significantly downregulated in GC. And the decreased expression of IRF6 was clinically correlated with poor prognosis of GC. Moreover, loss-of-function and gain-of-function studies showed that IRF6 was negatively regulated by ZEB1 but positively regulated by ELF3. Additionally, transcription factor ZEB1 and ELF3 could directly bind on IRF6 promoter, which suggested that transcription factor IRF6 is transcriptionally regulated by ZEB1 and ELF3. Nevertheless, we found that IRF6 expression was negatively related to its promoter methylation in TCGA stomach cancer cohorts. The downregulation of IRF6 in GC might be due to the overexpression of ZEB1 and the DNA methylation of IRF6 promoter.

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Section: Discussionmentioning

confidence: 98%

IRF6 Is Directly Regulated by ZEB1 and ELF3, and Predicts a Favorable Prognosis in Gastric Cancer

Cheng

Wang

et al. 2019

Front. Oncol.

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“…Our data suggest an interesting link between innate immune response and the normal epithelial differentiation program, which may be independent of immunity-related functions. This noncanonical role of interferons has been only in part investigated in the skin 27,28 and observed in the mammary gland 29,30 .…”

Section: Discussionmentioning

confidence: 99%

LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation

et al. 2019

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Though miR-205 function has been largely characterized, the nature of its host gene, MIR205HG, is still completely unknown. Here, we show that only lowly expressed alternatively spliced MIR205HG transcripts act as de facto pri-miRNAs, through a process that involves Drosha to prevent unfavorable splicing and directly mediate miR-205 excision. Notably, MIR205HG-specific processed transcripts revealed to be functional per se as nuclear long noncoding RNA capable of regulating differentiation of human prostate basal cells through control of the interferon pathway. At molecular level, MIR205HG directly binds the promoters of its target genes, which have an Alu element in proximity of the Interferon-Regulatory Factor (IRF) binding site, and represses their transcription likely buffering IRF1 activity, with the ultimate effect of preventing luminal differentiation. As MIR205HG functions autonomously from (albeit complementing) miR-205 in preserving the basal identity of prostate epithelial cells, it warrants reannotation as LEADeR (Long Epithelial Alu-interacting Differentiation-related RNA).

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“…Among the 42 overexpressed genes in our study, the majority (23 of 42) are associated with dysregulation of gene expression in one or more human cancers. These include, but are not limited to, FOSB [ 40 ], FOS [ 41 ], BMPR1B [ 42 ], WNT5A [ 43 , 44 ], PDPN [ 45 ], BMPER [ 46 ], IRF6 [ 47 ], and MYC [ 48 , 49 ]. Additionally, FOS, MYC, and PDPN have been shown to be overexpressed specifically in meningeal tumors [ 41 , 48 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

RNA-seq transcriptome analysis of formalin fixed, paraffin-embedded canine meningioma

et al. 2017

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Meningiomas are the most commonly reported primary intracranial tumor in dogs and humans and between the two species there are similarities in histology and biologic behavior. Due to these similarities, dogs have been proposed as models for meningioma pathobiology. However, little is known about specific pathways and individual genes that are involved in the development and progression of canine meningioma. In addition, studies are lacking that utilize RNAseq to characterize gene expression in clinical cases of canine meningioma. The primary objective of this study was to develop a technique for which high quality RNA can be extracted from formalin-fixed, paraffin embedded tissue and then used for transcriptome analysis to determine patterns of gene expression. RNA was extracted from thirteen canine meningiomas–eleven from formalin fixed and two flash-frozen. These represented six grade I and seven grade II meningiomas based on the World Health Organization classification system for human meningioma. RNA was also extracted from fresh frozen leptomeninges from three control dogs for comparison. RNAseq libraries made from formalin fixed tissue were of sufficient quality to successfully identify 125 significantly differentially expressed genes, the majority of which were related to oncogenic processes. Twelve genes (AQP1, BMPER, FBLN2, FRZB, MEDAG, MYC, PAMR1, PDGFRL, PDPN, PECAM1, PERP, ZC2HC1C) were validated using qPCR. Among the differentially expressed genes were oncogenes, tumor suppressors, transcription factors, VEGF-related genes, and members of the WNT pathway. Our work demonstrates that RNA of sufficient quality can be extracted from FFPE canine meningioma samples to provide biologically relevant transcriptome analyses using a next-generation sequencing technique, such as RNA-seq.

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IRF6 Is Involved in the Regulation of Cell Proliferation and Transformation in MCF10A Cells Downstream of Notch Signaling

Cited by 19 publications

References 38 publications

IRF6 Is Directly Regulated by ZEB1 and ELF3, and Predicts a Favorable Prognosis in Gastric Cancer

IRF6 Is Directly Regulated by ZEB1 and ELF3, and Predicts a Favorable Prognosis in Gastric Cancer

LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation

RNA-seq transcriptome analysis of formalin fixed, paraffin-embedded canine meningioma

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