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Epithelial to mesenchymal transition (EMT) is a process that allows epithelial cells to progressively acquire a reversible mesenchymal phenotype. Here, we recount the main events in the history of EMT. EMT was first studied during embryonic development. Nowadays, it is an important field in cancer research, studied all around the world by more and more scientists, because it was shown that EMT is involved in cancer aggressiveness in many different ways. The main features of EMT’s involvement in embryonic development, fibrosis and cancers are briefly reviewed here.

Our current view of DNA methylation processes is strongly moving: First, even if it was generally admitted that DNMT3A and DNMT3B are associated with de novo methylation and DNMT1 is associated with inheritance DNA methylation, these distinctions are now not so clear. Secondly, since one decade, many partners of DNMTs have been involved in both the regulation of DNA methylation activity and DNMT recruitment on DNA. The high diversity of interactions and the combination of these interactions let us to subclass the different DNMT-including complexes. For example, the DNMT3L/DNMT3A complex is mainly related to de novo DNA methylation in embryonic states, whereas the DNMT1/PCNA/UHRF1 complex is required for maintaining global DNA methylation following DNA replication. On the opposite to these unspecific DNA methylation machineries (no preferential DNA sequence), some recently identified DNMT-including complexes are recruited on specific DNA sequences. The coexistence of both types of DNA methylation (un/specific) suggests a close cooperation and an orchestration between these systems to maintain genome and epigenome integrities. Deregulation of these systems can lead to pathologic disorders.

The dynamics of colorectal epigenetics within the adenoma stages of oncogenesis remain undocumented. In this study, we investigated DNA methylation dynamics in colorectal cancer oncogenesis from non-tumor colon tissue to low-grade, high-grade adenoma and adenocarcinoma. The methylome of 12 low-grade and 19 high-grade colorectal adenomas was determined via the EPIC v1 Human Methylation BeadChip. These methylation profiles were complemented with the methylomes of 206 non-tumor colon and 22 colon adenocarcinoma samples from the GEO and TCGA databases. Differentially methylated CpGs were identified via Student’s t test and used to monitor the evolution of the colon methylome during oncogenesis. The differentially methylated promoters were used to infer the associated biological process via gene ontology and the evolution of the methylation of 34 described colorectal cancer DNA methylation biomarkers was explored. A total of 11.9% of the colon methylome was significantly altered (q < 10 − 4 ) during oncogenesis, with half corresponding to DNA demethylation. Of which, 67.4% occurred during the transition from non-tumor colon tissue to low-grade adenoma. A total of 9% of the DNA methylation changes were specific to low-grade and/or high-grade adenomas. The biological pathways related to the sensory perception of odor and stimulus were hypomethylated early, nucleic acid metabolic process were methylated early, post-transcriptional regulation were transiently hypomethylated and mitotic cell cycle were transiently methylated. Twenty-one out of 34 the biomarkers were methylated in low-grade adenomas and 11 out of 34 in high-grade adenomas. This suggests that they could be used to distinguish stages of oncogenesis. This study provides insight into the dynamics of colonic epigenetics during oncogenesis, with early DNA methylation changes in low-grade adenomas associated with transient DNA methylation changes. However, the causality of these changes remains to be elucidated. This study also explores the evolution of known biomarkers and their clinical applications for indirectly asserting the tumor’s stage.

Evidences highlight the role of various CD4 + helper T cells (CD4 + Th) subpopulations in orchestrating the immune responses against cancers. Epigenetics takes an important part in the regulation of CD4 + Th polarization and plasticity. In this review, we described the epigenetic factors that govern CD4 + T cells differentiation and recruitment in the tumor microenvironment and their subsequent involvement in the antitumor immunity. Finally, we discussed how to manipulate tumor reactive CD4 + Th responses by epigenetic drugs to improve anticancer immunotherapy.

For ten years, DNA methylation appeared as a major step in the understanding and issues of prostate cancers. Indeed, although classical biochemical parameters are still useful for prostate cancer diagnosis, they have poor sensitivity and are not specific for prostate cancer subtypes. The recent boom in the identification of specific DNA methylation profiles and the rapid development of liquid biopsies have completely modified the care of patients and may greatly influence outcomes in the future. Indeed, DNA methylation modifications could substantially improve the diagnosis by identifying specific prostate subtypes, improve follow-up to monitor residual disease, improve therapeutic efficiency by predicting the response to treatment, and improve the health quality of patients since these epigenetic modifications can easily be detected in non-invasive liquid biopsies.

The U6 snRNA, the core catalytic component of the spliceosome, is extensively modified post-transcriptionally, with 2’-O-methylation being most common. However, how U6 2’-O-methylation is regulated remains largely unknown. Here we report that TFIP11, the human homolog of the yeast spliceosome disassembly factor Ntr1, localizes to nucleoli and Cajal Bodies and is essential for the 2’-O-methylation of U6. Mechanistically, we demonstrate that TFIP11 knockdown reduces the association of U6 snRNA with fibrillarin and associated snoRNAs, therefore altering U6 2′-O-methylation. We show U6 snRNA hypomethylation is associated with changes in assembly of the U4/U6.U5 tri-snRNP leading to defects in spliceosome assembly and alterations in splicing fidelity. Strikingly, this function of TFIP11 is independent of the RNA helicase DHX15, its known partner in yeast. In sum, our study demonstrates an unrecognized function for TFIP11 in U6 snRNP modification and U4/U6.U5 tri-snRNP assembly, identifying TFIP11 as a critical spliceosome assembly regulator. In yeast, TFIP11 and DHX15 promote the disassembly of spliceosome complex after splicing is completed. Here the authors show that human TFIP11 functions independently of DHX15 and is required for U6 snRNA 2’-O-methylation and U4/U6.U5 tri-snRNP assembly.

Background Colorectal cancer is a public health issue and was the third leading cause of cancer-related death worldwide in 2022. Early diagnosis can improve prognosis, making screening a central part of colorectal cancer management. Blood-based screening, diagnosis and follow-up of colorectal cancer patients are possible with the study of cell-free circulating tumor DNA. This study aimed to identify novel DNA methylation biomarkers of colorectal cancer that can be used for the follow-up of patients with colorectal cancer. Methods A DNA methylation profile was established in the Gene Expression Omnibus (GEO) database ( n  = 507) using bioinformatics analysis and subsequently confirmed using The Cancer Genome Atlas (TCGA) database ( n  = 348). The in silico profile was then validated on local tissue and cell-free DNA samples using methylation-specific digital PCR in colorectal cancer patients ( n  = 35) and healthy donors ( n  = 35). Results The DNA methylation of COL25A1 and METAP1D was predicted to be a colorectal cancer biomarker by bioinformatics analysis (ROC AUC = 1, 95% CI [0.999–1]). The two biomarkers were confirmed with tissue samples, and the combination of COL25A1 and METAP1D yielded 49% sensitivity and 100% specificity for cell-free DNA. Conclusion Bioinformatics analysis of public databases revealed COL25A1 and METAP1D DNA methylation as clinically applicable liquid biopsies DNA methylation biomarkers. The specificity implies an excellent positive predictive value for follow-up, and the high sensitivity and relative noninvasiveness of a blood-based test make these biomarkers compatible with colorectal cancer screening. However, the clinical impact of these biomarkers in colorectal cancer screening and follow-up needs to be established in further prospective studies.

Pancreatic ductal adenocarcinoma (PDAC) is marked by molecular heterogeneity and poor prognosis. Among the stemness‐related transcription factors, Spalt‐like Transcription Factor 4 (SALL4) is correlated with unfavorable outcomes; however, its roles in PDAC remain unclear. SALL4high expression defines a PDAC subpopulation characterized by a shortened patient survival. Although SALL4 expression was mostly evaluated in tumor cells, our findings identify this embryonic transcription factor as a new biomarker in PDAC‐derived stroma. Gene expression analysis reveals that the SALL4high PDAC subset is enriched in cancer stem cell properties and stromal enrichment pathways; notably, an interaction with cancer‐associated fibroblasts (CAF) activated by TGF‐β. A particular oncogenic network was unraveled where Netrin‐1 and TGF‐β1 collaborate to induce SALL4 expression in CAF and drive their cancer‐stemness‐promoting functions. A 7‐gene stromal signature related to SALL4high PDAC samples was highlighted and validated by immunochemistry for prognosis and clinical application. This SALL4‐related stroma discriminated pancreatic preinvasive from invasive lesions and was enriched in short‐term survivors. Our results show that SALL4 transcriptional activity controls a molecular network defined by a specific stromal signature that characterizes PDAC invasiveness and worse clinical outcomes. Our findings identify the transcription factor SALL4 as a new biomarker in pancreatic cancer (PDAC)‐derived stroma. SALL4high PDAC subset is associated with poor prognosis. TGF‐β1 in collaboration with Netrin‐1 acts on fibroblast to promote SALL4 expression. SALL4 transcriptional activity controls a molecular network defined by a specific stromal signature that characterizes PDAC invasiveness and worse clinical outcomes.

Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer death worldwide, with no satisfactory treatment to date. In this study, we tested whether the combined inhibition of cyclooxygenase-2 (COX-2) and class I histone deacetylase (HDAC) may results in a better control of pancreatic ductal adenocarcinoma. The impact of the concomitant HDAC and COX-2 inhibition on cell growth, apoptosis and cell cycle was assessed first in vitro on human pancreas BxPC-3, PANC-1 or CFPAC-1 cells treated with chemical inhibitors (SAHA, MS-275 and celecoxib) or HDAC1/2/3/7 siRNA. To test the potential antitumoral activity of this combination in vivo, we have developed and characterized, a refined chick chorioallantoic membrane tumor model that histologically and proteomically mimics human pancreatic ductal adenocarcinoma. The combination of HDAC1/3 and COX-2 inhibition significantly impaired proliferation of BxPC-3 cells in vitro and stalled entirely the BxPC-3 cells tumor growth onto the chorioallantoic membrane in vivo. The combination was more effective than either drug used alone. Consistently, we showed that both HDAC1 and HDAC3 inhibition induced the expression of COX-2 via the NF-kB pathway. Our data demonstrate, for the first time in a Pancreatic Ductal Adenocarcinoma (PDAC) model, a significant action of HDAC and COX-2 inhibitors on cancer cell growth, which sets the basis for the development of potentially effective new combinatory therapies for pancreatic ductal adenocarcinoma patients.