Expression of ID4 protein in breast cancer cells induces reprogramming of tumour-associated macrophages

Donzelli, Sara; Milano, Elisa; Pruszko, Magdalena; Sacconi, Andrea; Masciarelli, Silvia; Iosue, Ilaria; Melucci, Elisa; Gallo, Enzo; Terrenato, Irene; Mottolese, Marcella; Żylicz, Maciej; Żylicz, Alicja; Fazi, Francesco; Blandino, Giovanni; Fontemaggi, Giulia

doi:10.1186/s13058-018-0990-2

Cited by 47 publications

(73 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ID4 has been demonstrated to be a member of a ribonucleoprotein complex along with mutant p53, SRSF1 and lncRNA MALAT1 (63). This complex promotes splicing of VEGFA pre-mRNA, which signals in a paracrine manner to macrophages and ultimately results in tumour angiogenesis (62,63,72). p53 and SRSF1 were not identified in our RIME analysis.…”

Section: Discussionmentioning

confidence: 80%

Proteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer

Baker

Holliday

Roden

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Basal-like breast cancer (BLBC) is a poorly characterised, heterogeneous disease. Patients are diagnosed with aggressive, high-grade tumours and often relapse with chemotherapy resistance. Detailed understanding of the molecular underpinnings of this disease is essential to the development of personalised therapeutic strategies. Inhibitor of Differentiation 4 (ID4) is a helix-loop-helix transcriptional regulator required for mammary gland development. ID4 is overexpressed in a subset of BLBC patients, associating with a stem-like poor prognosis phenotype, and is necessary for the growth of cell line models of BLBC, through unknown mechanisms. Methods Here, we have defined unique molecular insights into the function of ID4 in BLBC and the related disease high-grade serous ovarian cancer (HGSOC), by combining RIME proteomic analysis, ChIP-seq mapping of genomic binding sites and RNA-seq. Results These studies reveal novel interactions with DNA damage response proteins, in particular, mediator of DNA damage checkpoint protein 1 (MDC1). Through MDC1, ID4 interacts with other DNA repair proteins (γH2AX and BRCA1) at fragile chromatin sites. ID4 does not affect transcription at these sites, instead binding to chromatin following DNA damage. Analysis of clinical samples demonstrates that ID4 is amplified and overexpressed at a higher frequency in BRCA1 -mutant BLBC compared with sporadic BLBC, providing genetic evidence for an interaction between ID4 and DNA damage repair deficiency. Conclusions These data link the interactions of ID4 with MDC1 to DNA damage repair in the aetiology of BLBC and HGSOC.

show abstract

Section: Discussionmentioning

confidence: 80%

Proteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer

Baker

Holliday

Roden

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…HIF1α is a stimulator of TGF-β activity for cancer progression and metastasis (Joseph, Harishankar, Pillai, & Devi, 2018). HIF1 also trans-activate angiogenesis factors (Donzelli et al, 2018)…”

Section: Mammalian Target Of Rapamycin Complex 1 (Mtorc1)mentioning

confidence: 99%

Contribution of regulatory T cells to cancer: A review

Najafi

Farhood

Mortezaee

2018

Journal Cellular Physiology

160

103

View full text Add to dashboard Cite

Regulatory T cells (Tregs) represent a low number of T‐cell population under normal conditions, and they play key roles for maintaining immune system in homeostasis. The number of these cells is extensively increased in nearly all cancers, which is for dampening responses from immune system against cancer cells, metastasis, tumor recurrence, and treatment resistance. The interesting point is that apoptotic Tregs are stronger than their live counterparts for suppressing responses from immune system. Tregs within the tumor microenvironment have extensive positive cross‐talks with other immunosuppressive cells including cancer‐associated fibroblasts, cancer cells, macrophage type 2 cells, and myeloid‐derived suppressor cells, and they have negative interactions with immunostimulatory cells including cytotoxic T lymphocytes (CTL) and natural killer cells. A wide variety of markers are expressed in Tregs, among them forkhead box P3 (FOXP3) is the most specific marker and the master regulator of these cells. Multiple signals are activated by Tregs including transforming growth factor‐β, signal transducer and activator of transcription, and mTORC1. Treg reprogramming from an immunosuppressive to immunostimulatory proinflammatory phenotype is critical for increasing the efficacy of immunotherapy. This would be applicable through selective suppression of tumor‐bearing receptors in Tregs, including FOXP3, programmed death‐1, T‐cell immunoglobulin mucin‐3, and CTL‐associated antigen‐4, among others. Intratumoral Tregs can also be targeted by increasing the ratio for CTL/Treg.

show abstract

“…The miRNAs corresponding to 7 CG sites associated with HCC vascular infiltration (hsa‐miR‐200c, hsa‐miR‐345, hsa‐miR‐9‐1, hsa‐miR‐15b, hsa‐miR‐107, hsa‐miR‐199a‐3p, and hsa‐miR‐184) were screened with the LASSO‐Logistic method and are closely related to angiogenesis 38–42 . Ghosh et al 39 found that miR‐199a‐3p was directly involved in HCC angiogenesis, invasion, and metastasis, and it inhibits the angiogenesis of HCC by inhibiting the expression of VEGF and its receptor.…”

Section: Discussionmentioning

confidence: 99%

Screening and verification of microRNA promoter methylation sites in hepatocellular carcinoma

Lin

Dai

et al. 2020

J of Cellular Biochemistry

View full text Add to dashboard Cite

The promoter methylation mode of microribonucleic acid (miRNA) plays a crucial role in the process of hepatocellular carcinoma (HCC). Therefore, the primary purpose of this study was to screen and verify the miRNA methylation sites associated with the overall survival (OS) and clinical characteristics of HCC patients. Methylation-related data were from the Cancer Genome Atlas (TCGA). R software was utilized to screen the methylation sites. The least absolute shrinkage and selection operator algorithm was utilized to develop the miRNA promoter methylation models. Then, methylation-specific polymerase chain reaction was performed with 146 HCC tissues to verify the accuracy of the vascular infiltrationrelated model. Additionally, we verified the functions of vascular infiltration-related miRNA by utilizing cells transfected with miR-199a-3p mimic. The model for predicting OS of HCC patients contained eight methylation sites. The Kaplan-Meier analysis suggested that the model could divide HCC patients into high-and low-risk groups (P < .0001). COX regression analysis suggested that the model (P < .001; 95% CI, 1.264-2.709) and T category (P < .001; 95% CI, 1.472-3.119) were independent risk factors for affecting OS of HCC patients. The model for predicting vascular infiltration, pathological grade, and clinical stage contained 7, 10, and 9 methylation sites respectively, with their area under the receiver operating characteristic curve (AUC) values 0.667, 0.745, and 0.725, respectively. The functional analysis suggested that miRNA methylation is involved in various biological processes such as WNT, MAPK, and mTOR signaling pathways. The accuracy of the vascular infiltration-related model was consistent with our previous bioinformatics assay.And upregulation of miR-199a-3p decreased migration and invasion abilities. The screened miRNA promoter methylation sites can be served as biomarkers for judging OS, vascular infiltration, pathology grade, and clinical stage. It can also provide new targets for improving the treatment and prognosis of HCC patients. K E Y W O R D Sbioinformatics, hepatocellular carcinoma, miRNA, overall survival, promoter methylation, vascular infiltration Xiaofeng Ni, Zhuo Lin, and Shengjie Dai contributed equally to this study. SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.How to cite this article: Ni X, Lin Z, Dai S, et al. Screening and verification of microRNA promoter methylation sites in hepatocellular carcinoma.

show abstract

Expression of ID4 protein in breast cancer cells induces reprogramming of tumour-associated macrophages

Cited by 47 publications

References 61 publications

Proteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer

Proteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer

Contribution of regulatory T cells to cancer: A review

Screening and verification of microRNA promoter methylation sites in hepatocellular carcinoma

Contact Info

Product

Resources

About