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Activin A activation of Smad3 mitigates innate inflammation in mouse models of psoriasis and sepsis Thierry Gauthier et al. Phosphorylation of Smad3 is a critical mediator of TGF-β signaling, which plays an important role in regulating innate immune responses. However, whether Smad3 activation can be regulated in innate immune cells in TGF-β-independent contexts remains poorly understood. Here, we show that Smad3 is activated t... |
Atypical chemokine receptor 2 expression is directly regulated by hypoxia inducible factor-1 alpha in cancer cells under hypoxia Alice Benoit et al. Lack of significant and durable clinical benefit from anti-cancer immunotherapies is partly due to the failure of cytotoxic immune cells to infiltrate the tumor microenvironment. Immune infiltration is predominantly dependent on the chemokine network, which is regulated in part by chemokine and atypical chemokine re... |
MYB/LINC00092 regulatory axis promotes the progression of papillary thyroid carcinoma Cheng L. et al. Introduction:Thyroid carcinoma is the most frequent malignancy in different endocrine-related tumours. In this study, we demonstrated a long non-coding RNA LINC00092-associated molecular mechanism in promoting the progression of papillary thyroid carcinoma (PTC).
Material and methods:The expression of LINC00092 was... |
Substrate stiffness promotes vascular smooth muscle cell calcification by reducing the levels of nuclear actin monomers McNeill M.C. et al. Background: Vascular calcification (VC) is a prevalent independent risk factor for adverse cardiovascular events and is associated with diabetes, hypertension, chronic kidney disease, and atherosclerosis. However, the mechanisms regulating the osteogenic differentiation of vascular smooth muscle cells (VSMC) ar... |
DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks Pinto L.M. et al. Maintaining chromatin integrity at the repetitive non-coding DNA sequences underlying centromeres is crucial to prevent replicative stress, DNA breaks and genomic instability. The concerted action of transcriptional repressors, chromatin remodelling complexes and epigenetic factors controls transcription and chromat... |
CRISPR/Cas9-mediated inactivation of miR-34a and miR-34b/c inHCT116 colorectal cancer cells: comprehensive characterization afterexposure to 5-FU reveals EMT and autophagy as key processes regulatedby miR-34. Huang Z. et al. The miR-34a and miR-34b/c encoding genes represent direct targets of the p53 transcription factor, and presumably mediate part of the tumor suppressive effects of p53. Here, we sought to determine their functional relevance by inactivating miR-34a and/or miR-34b/c using a CRISPR/Cas9 approach in the colorectal cance... |
Curcumin activates a ROS/KEAP1/NRF2/miR-34a/b/c cascade tosuppress colorectal cancer metastasis. Liu C. et al. Curcumin, a natural phytochemical isolated from tumeric roots, represents a candidate for prevention and therapy of colorectal cancer/CRC. However, the exact mechanism of action and the downstream mediators of curcumin's tumor suppressive effects have remained largely unknown. Here we used a genetic approach to dete... |
miR-34a and IRE1A/XBP-1(S) Form a Double-NegativeFeedback Loop to Regulate Hypoxia-Induced EMT, Metastasis,Chemo-Resistance and Autophagy Bouznad N. et al. Tumor-associated hypoxia, i.e., decreased availability of oxygen, results in a poor clinical outcome since it promotes EMT, metastasis, and chemotherapy-resistance. We have previously identified p53 and its target miR-34a, as critical determinants of the effect of hypoxia on colorectal cancer (CRC). Here, we aimed t... |
Epigenetic regulation of plastin 3 expression by the macrosatelliteDXZ4 and the transcriptional regulator CHD4. Strathmann E. A. et al. Dysregulated Plastin 3 (PLS3) levels associate with a wide range of skeletal and neuromuscular disorders and the most common types of solid and hematopoietic cancer. Most importantly, PLS3 overexpression protects against spinal muscular atrophy. Despite its crucial role in F-actin dynamics in healthy cells and its i... |
Exploration of nuclear body-enhanced sumoylation reveals that PMLrepresses 2-cell features of embryonic stem cells. Tessier S. et al. Membrane-less organelles are condensates formed by phase separation whose functions often remain enigmatic. Upon oxidative stress, PML scaffolds Nuclear Bodies (NBs) to regulate senescence or metabolic adaptation. PML NBs recruit many partner proteins, but the actual biochemical mechanism underlying their pleiotropi... |
RAD51 protects human cells from transcription-replication conflicts. Bhowmick R. et al. Oncogene activation during tumorigenesis promotes DNA replication stress (RS), which subsequently drives the formation of cancer-associated chromosomal rearrangements. Many episodes of physiological RS likely arise due to conflicts between the DNA replication and transcription machineries operating simultaneously at... |
Epigenetic remodeling of downstream enhancer regions is linked toselective expression of the IL1F10 gene in differentiated humankeratinocytes. Talabot-Ayer D. et al. Interleukin (IL)-38, encoded by the IL1F10 gene, is a member of the IL-1 family of cytokines. IL-38 is constitutively expressed in epithelia in healthy humans, and in particular in epidermal keratinocytes in the skin. IL-38 expression is closely correlated with keratinocyte differentiation. The aim of this study was... |
Prolonged FOS activity disrupts a global myogenic transcriptionalprogram by altering 3D chromatin architecture in primary muscleprogenitor cells. Barutcu A Rasim et al. BACKGROUND: The AP-1 transcription factor, FBJ osteosarcoma oncogene (FOS), is induced in adult muscle satellite cells (SCs) within hours following muscle damage and is required for effective stem cell activation and muscle repair. However, why FOS is rapidly downregulated before SCs enter cell cycle as progenitor c... |
PARP1-SNAI2 transcription axis drives resistance to PARP inhibitor,Talazoparib. Ding X. et al. The synthetic lethal association between BRCA deficiency and poly (ADP-ribose) polymerase (PARP) inhibition supports PARP inhibitor (PARPi) clinical efficacy in BRCA-mutated tumors. PARPis also demonstrate activity in non-BRCA mutated tumors presumably through induction of PARP1-DNA trapping. Despite pronounced clin... |
AP4 suppresses DNA damage, chromosomal instability and senescence viainducing and repressing miR-22-3p Chou Jinjiang et al. Background AP4 (TFAP4) encodes a basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factor and is a direct target gene of the oncogenic transcription factor c-MYC. Here, we set out to determine the relevance of AP4 in human colorectal cancer (CRC) cells. Methods A CRISPR/Cas9 approach was employed to gene... |
Sevoflurane induces inflammation in primary hippocampal neurons byregulating Hoxa5/Gm5106/miR-27b-3p positive feedback loop. Zhu, Zifu and Ma, Li Postoperative cognitive dysfunction (POCD) is a normal condition that develops after surgery with anesthesia, leading to deterioration of cognitive functions. However, the mechanism of POCD still remains unknown. To elucidate the POCD molecular mechanism, sevoflurane was employed in the present study to generate neu... |
Regulatory interplay between Vav1, Syk and β-catenin occurs in lungcancer cells. Boudria Rofia et al. Vav1 exhibits two signal transducing properties as an adaptor protein and a regulator of cytoskeleton organization through its Guanine nucleotide Exchange Factor module. Although the expression of Vav1 is restricted to the hematopoietic lineage, its ectopic expression has been unraveled in a number of solid tumors. ... |
Epigenetic remodelling of enhancers in response to estrogen deprivationand re-stimulation. Sklias Athena et al. Estrogen hormones are implicated in a majority of breast cancers and estrogen receptor alpha (ER), the main nuclear factor mediating estrogen signaling, orchestrates a complex molecular circuitry that is not yet fully elucidated. Here, we investigated genome-wide DNA methylation, histone acetylation and transcriptio... |
Enhanced targeted DNA methylation of the CMV and endogenous promoterswith dCas9-DNMT3A3L entails distinct subsequent histonemodification changes in CHO cells. Marx Nicolas et al. With the emergence of new CRISPR/dCas9 tools that enable site specific modulation of DNA methylation and histone modifications, more detailed investigations of the contribution of epigenetic regulation to the precise phenotype of cells in culture, including recombinant production subclones, is now possible. These al... |
Atg7 deficiency in microglia drives an altered transcriptomic profileassociated with an impaired neuroinflammatory response Friess L. et al. Microglia, resident immunocompetent cells of the central nervous system, can display a range of reaction states and thereby exhibit distinct biological functions across development, adulthood and under disease conditions. Distinct gene expression profiles are reported to define each of these microglial reaction stat... |
FOS licenses early events in stem cell activation driving skeletal muscleregeneration. Almada, Albert E. et al. Muscle satellite cells (SCs) are a quiescent (non-proliferative) stem cell population in uninjured skeletal muscle. Although SCs have been investigated for nearly 60 years, the molecular drivers that transform quiescent SCs into the rapidly dividing (activated) stem/progenitor cells that mediate muscle repair after ... |
CREB3 Transactivates lncRNA ZFAS1 to Promote PapillaryThyroid Carcinoma Metastasis by Modulating miR-373-3/MMP3Regulatory Axis Wang G. et al. The incidence rate of thyroid carcinoma ranks ninth among human malignancies, and it accounts for the most frequent malignancy in endocrine-related tumors. This study aimed to investigate the role of long noncoding RNA (lncRNA) ZFAS1 in the metastasis of papillary thyroid carcinoma (PTC) and the potential molecular ... |
The transcription factor scleraxis differentially regulates gene expressionin tenocytes isolated at different developmental stages. Paterson, YZ and Evans, N and Kan, S and Cribbs, A and Henson, FMD andGuest, DJ The transcription factor scleraxis (SCX) is expressed throughout tendon development and plays a key role in directing tendon wound healing. However, little is known regarding its role in fetal or young postnatal tendons, stages in development that are known for their enhanced regenerative capabilities. Here we used ... |
TET-Mediated Hypermethylation Primes SDH-Deficient Cells for HIF2α-Driven Mesenchymal Transition. Morin A, Goncalves J, Moog S, Castro-Vega LJ, Job S, Buffet A, Fontenille MJ, Woszczyk J, Gimenez-Roqueplo AP, Letouzé E, Favier J Loss-of-function mutations in the SDHB subunit of succinate dehydrogenase predispose patients to aggressive tumors characterized by pseudohypoxic and hypermethylator phenotypes. The mechanisms leading to DNA hypermethylation and its contribution to SDH-deficient cancers remain undemonstrated. We examine th... |
The nuclear hypoxia-regulated NLUCAT1 long non-coding RNA contributes to an aggressive phenotype in lung adenocarcinoma through regulation of oxidative stress. Moreno Leon L, Gautier M, Allan R, Ilié M, Nottet N, Pons N, Paquet A, Lebrigand K, Truchi M, Fassy J, Magnone V, Kinnebrew G, Radovich M, Cheok MH, Barbry P, Vassaux G, Marquette CH, Ponzio G, Ivan M, Pottier N, Hofman P, Mari B, Rezzonico R Lung cancer is the leading cause of cancer death worldwide, with poor prognosis and a high rate of recurrence despite early surgical removal. Hypoxic regions within tumors represent sources of aggressiveness and resistance to therapy. Although long non-coding RNAs (lncRNAs) are increasingly recognized as major gene ... |
Elevated cyclic-AMP represses expression of exchange protein activated by cAMP (EPAC1) by inhibiting YAP-TEAD activity and HDAC-mediated histone deacetylation. Ebrahimighaei R, McNeill MC, Smith SA, Wray JP, Ford KL, Newby AC, Bond M Ligand-induced activation of Exchange Protein Activated by cAMP-1 (EPAC1) is implicated in numerous physiological and pathological processes, including cardiac fibrosis where changes in EPAC1 expression have been detected. However, little is known about how EPAC1 expression is regulated. Therefore, we investigated r... |
Adolescent social isolation affects parvalbumin expression in the medial prefrontal cortex in the MAM-E17 model of schizophrenia. Maćkowiak M, Latusz J, Głowacka U, Bator E, Bilecki W Altered parvalbumin (PV) expression is observed in the prefrontal cortex of subjects with schizophrenia. Environmental context, particularly during adolescence, might regulate PV expression. In the present study, we investigated the effect of adolescent social isolation (SI) on PV expression in the medial prefrontal... |
Enhancers in the Peril lincRNA locus regulate distant but not local genes. Groff AF, Barutcu AR, Lewandowski JP, Rinn JL BACKGROUND: Recently, it has become clear that some promoters function as long-range regulators of gene expression. However, direct and quantitative assessment of enhancer activity at long intergenic noncoding RNA (lincRNA) or mRNA gene bodies has not been performed. To unbiasedly assess the enhancer capacity across... |