E2F transcription factor 2-activated DLEU2 contributes to prostate tumorigenesis by upregulating serum and glucocorticoid-induced protein kinase 1

Li, Peizhang; Xu, Huan; Liu, Yang; Zhan, Ming; Shi, Yuanping; Zhang, Cao-Xu; Gao, Dongyue; Gu, Meng; Chen, Yanbo; Wang, Zhong

doi:10.1038/s41419-022-04525-1

Cited by 15 publications

(13 citation statements)

References 40 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, by comparing the differences in the functional enrichment of luminal cells between the TZ and PZ, we found that luminal cells in the PZ expressed higher levels of MYC and E2F target genes, androgen/lineage and DNA repair genes. Excessive activation of the MYC and E2F pathways and their regulated genes have been considered to be an important event in the malignant degeneration of prostate luminal cells, 46 , 47 which may be one of the reasons why luminal cells in the PZ are more susceptible to malignancy.…”

Section: Discussionmentioning

confidence: 99%

Single‐cell RNA‐sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zone

Yan

Wang

Xia

et al. 2022

Clinical & Translational Med

View full text Add to dashboard Cite

Background Identifying cellular and functional heterogeneity within aged prostate is critical for understanding the spatial distribution of prostate diseases. Methods Aged human prostate peripheral zone (PZ) and transitional zone (TZ) tissues were used for single‐cell RNA‐sequencing. Results were validated by immunofluorescence staining. Results We found that club/hillock epithelial cells, compared with other epithelial cells, had significantly higher NOTCH signaling activity and expressed higher levels of neuro‐stems but lower androgen‐related genes. These cells were primarily found in the TZ and provided a stem‐like niche around the proximal prostate ducts. Significant heterogeneity was observed in the aged luminal population. A novel TFF3+ luminal subtype with elevated MYC and E2F pathway activities was observed, primarily in the PZ. Further analysis revealed that epithelial cells in the TZ had higher levels of stem‐ and inflammation‐related pathway activities but lower androgen/lineage‐related pathway activities than those in the PZ. Notably, the activation of MYC, E2F and DNA repair pathways significantly increased in PZ luminal cells. In the immune landscape, we found that the immune microenvironment in the TZ is more complex and disordered with more infiltration of NK and Treg cells. CD8 T cell and macrophage in the TZ exhibit both inflammation activation and suppression phenotypes. In the stroma, the TZ had a higher fibroblast density, and fibroblasts in the TZ exhibited stronger transcriptome activity in immunity and proliferation. Ligand–receptor interaction analysis revealed that fibroblasts could contribute to a NOTCH signaling niche for club/hillock cells in the TZ and balance the prostate immune microenvironment. The activation of stem properties, inflammatory infiltration and loss of androgen/lineage activity are prominent features distinguishing the TZ from PZ. Conclusions Our study explains the heterogeneity between the TZ and PZ of aged prostate, which may help understand the spatial distribution of prostate diseases and establish a foundation for novel target discovery.

show abstract

Section: Discussionmentioning

confidence: 99%

Single‐cell RNA‐sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zone

Yan

Wang

Xia

et al. 2022

Clinical & Translational Med

View full text Add to dashboard Cite

show abstract

“…On the one hand, miR‐582‐5p was reported to repress TGF‐β signaling by directly inhibiting SMAD2 and facilitate NF‐κB pathway by inhibiting CREB, 26,27 both of which might promote inflammation. On the other hand, miR‐582‐5p was also reported to downregulate the expression of HMGB1, EZH2 and SGK1, 28–30 which were previously reported to promote colitis in animal model or clinical samples 31–33 . It is noteworthy that studies mentioned above were all conducted in cancer cell lines.…”

Section: Discussionmentioning

confidence: 96%

Peripheral blood mononuclear cell microRNAs are novel biomarkers for diagnosing and monitoring Crohn's disease

Chen

et al. 2022

The FASEB Journal

View full text Add to dashboard Cite

Crohn's disease is a recurrent, progressive, immune‐mediated inflammatory disease and merely manifests non‐specific symptoms at early stage. In this study, we isolated peripheral blood mononuclear cells (PBMCs) to determine whether PBMC miRNAs are reliable biomarkers for Crohn's disease diagnosing and monitoring. 5 Crohn's disease patients and 5 healthy controls were recruited to find differentially expressed miRNAs by next generation sequencing. Candidate PBMC miRNAs were further validated by qRT‐PCR in another cohort consisting of 86 Crohn's disease patients and 39 healthy controls. We found PBMC miR‐582‐5p could diagnose Crohn's disease with the area under receiver operating characteristic curve (AUROC) of 0.701(95%CI 0.606–0.796, p < .001). While PBMC miR‐96‐5p was significantly higher in active Crohn's disease and correlated with both clinical (ρ = 0.376, p < .001) and endoscopic activity (ρ = 0.512, p = .015). Furthermore, PBMC miR‐96‐5p had a better performance in recognizing active Crohn's disease with AUROC of 0.727 (95%CI 0.609–0.844, p = .001) than C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR) and fecal calprotectin. In conclusion, PBMC miR‐582‐5p may be further utilized as a diagnostic biomarker, while miR‐96‐5p may be a novel and valuable biomarker in monitoring disease activity.

show abstract

“…DLEU2 is the host gene for miR15a/16–1, it regulates B cell proliferation and has been reported to be deleted or epigenetically suppressed in leukemia (Mertens et al, 2006 ; Lerner et al, 2009 ; Klein et al, 2010 ). Previous studies have reported that DLEU2 is expressed in various cell types including immune cells such as B cells and T cells and mainly localized in the cytoplasm (He et al, 2021 , 2; Li et al, 2022 , 2; Dong et al, 2021 ), suggesting that it may have the potential to be translated into protein.…”

Section: Discussionmentioning

confidence: 99%

A lncRNA Dleu2-encoded peptide relieves autoimmunity by facilitating Smad3-mediated Treg induction

Tang,

Zhang,

Lou

et al. 2024

EMBO Rep

View full text Add to dashboard Cite

Micropeptides encoded by short open reading frames (sORFs) within long noncoding RNAs (lncRNAs) are beginning to be discovered and characterized as regulators of biological and pathological processes. Here, we find that lncRNA Dleu2 encodes a 17-amino-acid micropeptide, which we name Dleu2-17aa, that is abundantly expressed in T cells. Dleu2-17aa promotes inducible regulatory T (iTreg) cell generation by interacting with SMAD Family Member 3 (Smad3) and enhancing its binding to the Foxp3 conserved non-coding DNA sequence 1 (CNS1) region. Importantly, the genetic deletion of Dleu2-17aa in mice by start codon mutation impairs iTreg generation and worsens experimental autoimmune encephalomyelitis (EAE). Conversely, the exogenous supplementation of Dleu2-17aa relieves EAE. Our findings demonstrate an indispensable role of Dleu2-17aa in maintaining immune homeostasis and suggest therapeutic applications for this peptide in treating autoimmune diseases.

show abstract

E2F transcription factor 2-activated DLEU2 contributes to prostate tumorigenesis by upregulating serum and glucocorticoid-induced protein kinase 1

Cited by 15 publications

References 40 publications

Single‐cell RNA‐sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zone

Single‐cell RNA‐sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zone

Peripheral blood mononuclear cell microRNAs are novel biomarkers for diagnosing and monitoring Crohn's disease

A lncRNA Dleu2-encoded peptide relieves autoimmunity by facilitating Smad3-mediated Treg induction

Contact Info

Product

Resources

About