FOXA1 defines cancer cell specificity

Zhang, Gaihua; Zhao, Yongbing; Liu, Yi; Kao, Li Pin; Wang, Xiao; Skerry, Benjamin; Li, Zhaoyu

doi:10.1126/sciadv.1501473

Cited by 43 publications

(45 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Su(z)12 is part of the ubiquitous polycomb repressive complex 2 (PRC2) and is overexpressed in numerous cancers, including gastric cancer where Su(z)12 levels were associated with increased metastasis and unfavorable survival prognosis 67 . The ETS family of transcription factors has demonstrated significant involvement in all stages of tumorigenesis 68 , while FoxA1 is known as ‘pioneer transcription factor in organogenesis and cancer progression’ 69 . Finally, ULK2 is an autophagy regulator overexpressed in prostate cancer cells 70 .…”

Section: Resultsmentioning

confidence: 99%

Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells

Mihaylova

Abnave

Kao

et al. 2017

Preprint

View full text Add to dashboard Cite

Background 21The family of Mixed Lineage Leukaemia (MLL) histone methyltransferase 22 proteins is often implicated in disease processes, particularly cancer. We 23 focus on the tumour suppressors MLL3 and MLL4, which are mutated in a 24 high percentage of cancers, but very little is known about the underlying 25 transcriptional and epigenetic changes that contribute to malignancy. 26 Results 27Here we make use of the highly accessible planarian model system to 28 uncover a role for MLL3/4 orthologs in controlling stem cell differentiation 29 and proliferation, suggesting conservation of tumour suppressor function 30 over a large evolutionary timescale for these epigenetic regulators. 31Knockdown of the planarian Mll3/4 orthologs compromises stem cell 32 differentiation and leads to hyper-proliferation and tumour-like outgrowth 33formation. The planarian system allows us to investigate the early-stage 34 epigenetic and transcriptional changes in cells that will go on to form 35 tumours after loss of MLL3/4 function, identifying genome wide alterations 36 that occur early in the development of the pathology. This reveals mis-37 regulation of both conserved and hypothesised oncogenes and tumour 38 suppressors, that together likely explain the cancer-like phenotype 39 observed in planarians. 40 Conclusions 41We confirm MLL3/4 tumour suppressor function and uncover a deep 42 conservation of this role in stem cells. We find potentially conserved mis-43 regulated downstream targets driving the effects of MLL3/4 loss of function. 44Our work demonstrates the suitability of planarians for the study of 45 epigenetic phenotypes related to cancer and stem cell function, and for 46 capturing early causative changes in a definitive population of tumour 47 forming stem cells in vivo. 48 49 50 51. CC-BY-NC 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/126540 doi: bioRxiv preprint first posted online Apr. 11, 2017; 52 53 Background 54The pluripotent adult stem cell (pASC) population of planarian flatworms is a 55 highly accessible study system to elucidate fundamental aspects of stem cell 56 function 1,2 . These stem cells, collectively known as neoblasts (NBs), bestow 57 these animals with an endless capacity to regenerate all the organs and 58 tissues of this relatively simple organism after amputation. Comparisons of 59 stem cell expression profiles and available functional data between planarians 60 and other simpler animals with mammals show that key aspects of stem cell 61 biology are deeply conserved [3][4][5][6][7][8][9] . Thus, studies of the NB population have the 62 potential to inform us about the origins of fundamental stem cell properties 63 and behaviors such as maintenance of genome stability 10 , self-renewal 7,11 , 64 pluripotency 12-15 , differentiation [16][17][18] and migration 19,20 . All of these are highl...

show abstract

Section: Resultsmentioning

confidence: 99%

Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells

Mihaylova

Abnave

Kao

et al. 2017

Preprint

View full text Add to dashboard Cite

show abstract

“…FOXA1 was also related to diverse biological processes like phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway, DNA methylation cancer cell specificity. 12,23,24 However, no report has mentioned the function of miR-194 and FOXA1 in neuropathic pain so far. Therefore, we speculated an effect of miR-194 on neuropathic pain process.…”

Section: Discussionmentioning

confidence: 99%

“…FOXA1 was reported to form cell-specific genomic signature and regulate gene expression in many ways, defining cancer cell specificity in various human cancer cells. 12 FOXA1 was also involved in liver cancer, breast cancer. 18,14,15 But there was no report that showed the function of FOXA1 in neuropathic pain.…”

Section: Introductionmentioning

confidence: 99%

miR‐194 relieve neuropathic pain and prevent neuroinflammation via targeting FOXA1

Zhang

Chen

Shen

et al. 2020

J of Cellular Biochemistry

View full text Add to dashboard Cite

The emerging role of microRNAs (miRNAs) have been deeply explored in multiple diseases including neuropathic pain. miR-194 was widely reported to be a tumor suppressor and was related to the inflammatory response. The critical role of neuroinflammation on neuropathic pain leads to a thinking about the relationship between miR-194 and neuropathic pain. However, the function of miR-194 in neuropathic pain remains unknown. This study was aimed to explore the relationship between miR-194 and neuropathic pain progression by chronic sciatic nerve injury (CCI). miR-194 abnormally downregulated in the CCI model rat and its overexpression significantly alleviates neuroinflammation in vivo. We predict Forkhead box protein A1 (FOXA1) as a direct target of miR-194, whose restoration can markedly reverse the effects of miR-194 on neuropathic pain. Overall, our study demonstrated a novel mechanism of neuropathic pain progression that miR-194 alleviates neuropathic pain via targeting FOXA1 and preventing neuroinflammation by downregulating inflammatory cytokines containing cyclooxygenase 2, interleukin 6 (IL-6), and IL-10 in vivo, which can be reversed by the overexpression of FOXA1. , miR-194, neuroinflammation, neuropathic pain K E Y W O R D S FOXA1

show abstract

“…In addition to directly regulating transcription, studies show TFs regulate gene expression through epigenetic histone modifications and open chromatin accessibility in breast cancers [21][22][23][24]. However, a comprehensive understanding of how TF repertoire, epigenetic open chromatin TF accessibility, histone modifications and 3D genome architecture that allows for subtype expression and hence its distinction is not well understood.…”

Section: Introductionmentioning

confidence: 99%

Subtype-specific epigenomic landscape and 3D genome structure in bladder cancer

Iyyanki

Zhang

Jin

et al. 2020

Preprint

View full text Add to dashboard Cite

Muscle-invasive bladder cancers have recently been characterized by their distinct expression of luminal and basal genes, which could be used to predict key clinical features such as disease progression and overall survival. For example, FOXA1, GATA3, and PPARG have been shown to be essential for luminal subtype-specific regulation and subtype switching, while TP63 and STAT3 are critical for basal subtype bladder cancer. Despite these advances, the underlying epigenetic mechanism and 3D chromatin architecture for subtypespecific regulation in bladder cancers remains largely unknown. Here, we determined the genome-wide transcriptome, enhancer landscape, TF binding profiles (FOXA1 and GATA3) in luminal and basal subtypes of bladder cancers. Furthermore, we mapped genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors, for the first time in bladder cancer. We showed that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct TF binding at distal-enhancers of luminal and basal bladder cancers. Finally, we identified a novel clinically relevant transcriptional factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other luminal-specific genes (such as FOXA1, GATA3, and PPARG) and affects cancer cell proliferation and migration. In summary, our work shows a subtype-specific epigenomic and 3D genome structure in urinary bladder cancers and suggested a novel link between the circadian TF NPAS2 and a clinical bladder cancer subtype.

show abstract

FOXA1 defines cancer cell specificity

Cited by 43 publications

References 39 publications

Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells

Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells

miR‐194 relieve neuropathic pain and prevent neuroinflammation via targeting FOXA1

Subtype-specific epigenomic landscape and 3D genome structure in bladder cancer

Contact Info

Product

Resources

About