LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: May 7, 2022

LncRNA-PACERR plays critical role in the polarization of tissue-associated macrophages (TAMs). In this study, we found function and molecular mechanism PACERR TAMs to regulate pancreatic ductal adenocarcinoma (PDAC) progression.We used qPCR analyse expression M1-tissue-resident (M1-NTRMs) which were isolated from 46 PDAC tissues. The on proliferation, migration invasion confirmed through vivo vitro assays. was discussed via fluorescence situ hybridization (FISH), RNA pull-down, ChIP-qPCR, RIP-qPCR luciferase assays.LncRNA-PACERR high associated with poor prognosis patients. Our finding validated that increased number M2-polarized cells facilized cell vivo. Mechanistically, activate KLF12/p-AKT/c-myc pathway by binding miR-671-3p. And bound IGF2BP2 acts as an m6A-dependent manner enhance stability KLF12 c-myc cytoplasm. addition, promoter a target recruited EP300 increase acetylation histone interacting nucleus.This study functions key regulator microenvironment revealed novel mechanisms cytoplasm nucleus.

Language: Английский

---

HCC-Related lncRNAs: Roles and Mechanisms

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(1), P. 597 - 597

Published: Jan. 2, 2024

Hepatocellular carcinoma (HCC) presents a significant global health threat, particularly in regions endemic to hepatitis B and C viruses, because of the ongoing pandemic obesity causing metabolic-dysfunction-related fatty liver disease (MAFLD), precursor HCC. The molecular intricacies HCC, genetic epigenetic alterations, dysregulated signaling pathways facilitate personalized treatment strategies based on profiling. Epigenetic regulation, encompassing DNA methyltion, histone modifications, noncoding RNAs, functions as critical layer influencing HCC development. Long RNAs (lncRNAs) are spotlighted for their diverse roles gene regulation potential diagnostic therapeutic tools cancer. In this review, we explore pivotal role lncRNAs including MAFLD viral hepatitis, most prevalent risk factors hepatocarcinogenesis. dysregulation is implicated progression by modulating chromatin transcription, sponging miRNAs, structural functions. studies contribute deeper comprehension pathogenesis offer promising routes precision medicine, highlighting utility early biomarkers, prognostic indicators, targets.

Language: Английский

---

CXCL12/CXCR4: An amazing challenge and opportunity in the fight against fibrosis

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 83, P. 101809 - 101809

Published: Nov. 25, 2022

Language: Английский

---

LncRNA NEAT1 : Shedding light on mechanisms and opportunities in liver diseases

Liver International, Journal Year: 2020, Volume and Issue: 40(11), P. 2612 - 2626

Published: Aug. 3, 2020

With advances in genome and transcriptome research technology, the function mechanism of lncRNAs physiological pathological states have been gradually revealed. Nuclear Enriched Abundant Transcript 1 (NEAT1, a long non-coding RNA), vital component paraspeckles, plays an indispensable role formation integrity paraspeckles. Throughout history, NEAT1 is mostly aberrantly upregulated various cancers, high expression often contributes to poor prognosis patients. Notably, liver diseases increasingly reported. accelerates progression non-alcoholic fatty disease (NAFLD), fibrosis hepatocellular carcinoma, while exerting protective pathogenesis acute-on-chronic failure by inhibiting inflammatory response. In this review, we will elaborate on relevant studies different casting diseases, especially focusing its regulatory mechanisms new opportunities for alcoholic disease.

Language: Английский

---

Noncoding RNAs in Nonalcoholic Fatty Liver Disease: Potential Diagnosis and Prognosis Biomarkers

Disease Markers, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 16

Published: Aug. 27, 2020

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic worldwide in part due to concomitant obesity pandemic and insulin resistance (IR). It increasingly becoming evident that NAFLD a affecting numerous extrahepatic vital organs regulatory pathways. The molecular mechanisms underlying nonalcoholic steatosis formation are poorly understood, little information available on pathways responsible for progressive hepatocellular damage follows lipid accumulation. Recently, much research has focused identification of epigenetic modifications contribute pathogenesis. Noncoding RNAs (ncRNAs) one such factors could be implicated development progression. In this review, we summarize current knowledge genetic potentially disease. Particular emphasis will put contribution microRNAs (miRNAs), long noncoding (lncRNAs), circular (circRNAs) pathophysiology as well their potential use therapeutic targets or markers prediction progression

Language: Английский

---

EndMT Regulation by Small RNAs in Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: May 19, 2021

Diabetes-associated complications, such as retinopathy, nephropathy, cardiomyopathy, and atherosclerosis, the main consequences of long-term hyperglycemia, often lead to organ dysfunction, disability, increased mortality. A common denominator these complications is myofibroblast-driven excessive deposition extracellular matrix proteins. Although fibroblast appears be primary source myofibroblasts, other cells, including endothelial can generate myofibroblasts through a process known mesenchymal transition (EndMT). During EndMT, cells lose their typical phenotype acquire features, characterized by development invasive migratory abilities well expression products α-smooth muscle actin type I collagen. EndMT involved in many chronic fibrotic diseases regulated complex molecular mechanisms different signaling pathways. Recent evidence suggests that small RNAs, particular microRNAs (miRNAs) long non-coding RNAs (lncRNAs), are crucial mediators EndMT. Furthermore, miRNAs both affected oxidative stress, another key player pathophysiology diabetic complications. In this review, we provide an overview redox signals underpinning diabetic-associated process. Then, discuss current knowledge on role regulation atherosclerosis highlight potential links between stress dyad RNAs-EndMT driving pathological states.

Language: Английский

---

Interplay Between GH-regulated, Sex-biased Liver Transcriptome and Hepatic Zonation Revealed by Single-Nucleus RNA Sequencing

Endocrinology, Journal Year: 2022, Volume and Issue: 163(7)

Published: May 4, 2022

Abstract The zonation of liver metabolic processes is well-characterized; however, little known about the cell type-specificity and sexually dimorphic gene expression or its growth hormone (GH)-dependent transcriptional regulators. We address these issues using single-nucleus RNA-sequencing 32 000 nuclei representing 9 major types. Nuclei were extracted from livers adult male female mice; males infused with GH continuously, mimicking plasma pattern; mice exposed to TCPOBOP, a xenobiotic agonist ligand nuclear receptor CAR that perturbs sex-biased expression. Analysis rich transcriptomic datasets revealed following: 1) genes their GH-dependent regulators primarily restricted hepatocytes not feature nonparenchymal cells; 2) many transcripts show sex-dependent within lobule; 3) substantially feminized both in periportal pericentral when are continuously; 4) sequencing increases sensitivity for detecting thousands nuclear-enriched long-noncoding RNAs (lncRNAs) enables determination type-specificity, sex-bias hepatocyte profiles; 5) ratio significantly higher than liver; 6) TCPOBOP exposure disrupts sex-specific lobule. These findings highlight complex interconnections between hepatic sexual dimorphism at single-cell level reveal how endogenous hormones foreign chemical can alter interactions across lobule large effects on protein-coding lncRNAs.

Language: Английский

---

Epigenetic modification in liver fibrosis: Promising therapeutic direction with significant challenges ahead

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(3), P. 1009 - 1029

Published: Nov. 4, 2023

Liver fibrosis, characterized by scar tissue formation, can ultimately result in liver failure. It's a major cause of morbidity and mortality globally, often associated with chronic diseases like hepatitis or alcoholic non-alcoholic fatty diseases. However, current treatment options are limited, highlighting the urgent need for development new therapies. As reversible regulatory mechanism, epigenetic modification is implicated many biological processes, including fibrosis. Exploring mechanisms involved fibrosis could provide valuable insights into developing treatments diseases, although evidence still controversial. This review provides comprehensive summary critical targets modifications, DNA methylation, histone modification, RNA fibrotic The potential cooperation different modifications promoting fibrogenesis was also highlighted. Finally, available agonists inhibitors regulating these their application preventing were discussed. In summary, elucidating specific druggable more selective candidate medicines may represent promising approach bright prospects

Language: Английский

---

Construction of a novel MPT-driven necrosis-related lncRNAs signature for prognosis prediction in laryngeal squamous cell carcinoma

Environmental Science and Pollution Research, Journal Year: 2023, Volume and Issue: 30(31), P. 77210 - 77225

Published: May 30, 2023

Language: Английский

---

Long Noncoding RNA VLDLR-AS1 Levels in Serum Correlate with Combat-Related Chronic Mild Traumatic Brain Injury and Depression Symptoms in US Veterans

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1473 - 1473

Published: Jan. 25, 2024

More than 75% of traumatic brain injuries (TBIs) are mild (mTBI) and military service members often experience repeated combat-related mTBI. The chronic comorbidities concomitant with repetitive mTBI (rmTBI) include depression, post-traumatic stress disorder or neurological dysfunction. This study sought to determine a long noncoding RNA (lncRNA) expression signature in serum samples that correlated rmTBI years after the incidences. Serum were obtained from Long-Term Impact Military-Relevant Brain-Injury Consortium Chronic Effects Neurotrauma (LIMBIC CENC) repository, participants unexposed TBI who had rmTBI. Four lncRNAs identified as consistently present all samples, detected via droplet digital PCR packaged exosomes enriched for CNS origin. results, using qPCR, demonstrated lncRNA VLDLR-AS1 levels significantly lower among individuals compared those no lifetime TBI. ROC analysis determined an AUC 0.74 (95% CI: 0.6124 0.8741; p = 0.0012). optimal cutoff was ≤153.8 ng. A secondary clinical data LIMBIC CENC conducted evaluate psychological symptom burden, results show MALAT1 symptoms depression. In conclusion, may serve blood biomarker identifying depression patients.

Language: Английский

---