Hepatocyte-derived exosomal miR-146a-5p inhibits hepatic stellate cell EMT process: a crosstalk between hepatocytes and hepatic stellate cells DOI Creative Commons

Zhichao Lang,

Yifei Li,

Lifan Lin

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Aug. 19, 2023

Recently, Salidroside (Sal) has been demonstrated to suppress hepatic stellate cell (HSC) activation, a crucial event for liver fibrosis. Moreover, Sal reported decrease hepatocyte injury. A growing number of reports have indicated that the crosstalk between hepatocytes and HSCs is very fibrosis development. Whether Sal-treated could inhibit HSC activation unclear. Exosomes, as vital vehicles intercellular communication, shown transfer cargos HSCs. Herein, we aimed investigate roles exosomal miRNAs from in well Our results showed suppressed carbon tetrachloride (CCl4)-induced vivo. proliferation was repressed co-cultured with hepatocytes. Interestingly, miR-146a-5p up-regulated by CCl4-treated mice. Also, enhanced found isolated CCl4 mice hepatocyte-derived exosomes. Notably, contributed inactivation. Inhibiting exosomes resulted reduced E-cadherin (E-cad) increased desmin HSCs, indicating caused inactivation via epithelial-mesenchymal transition (EMT). inhibition-mediated EMT process were blocked down loss EIF5A2. Further studies revealed EIF5A2 target miR-146a-5p. Furthermore, overexpression inhibited Collectively, inhibits fibrosis, at least part, suppressing process.

Language: Английский

MEG3: an Oncogenic Long Non-coding RNA in Different Cancers DOI

Arwa Al-Rugeebah,

Mohammed Alanazi,

Narasimha Reddy Parine

et al.

Pathology & Oncology Research, Journal Year: 2019, Volume and Issue: 25(3), P. 859 - 874

Published: Feb. 21, 2019

Language: Английский

Citations

177
Role of miRNA and lncRNAs in organ fibrosis and aging DOI Open Access
Soudeh Ghafouri‐Fard, Atefe Abak,

Seyedeh Fahimeh Talebi

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 143, P. 112132 - 112132

Published: Sept. 1, 2021

Fibrosis is the endpoint of pathological remodeling. This process contributes to pathogenesis several chronic disorders and aging-associated organ damage. Different molecular cascades contribute this process. TGF-β, WNT, YAP/TAZ signaling pathways have prominent roles in A number long non-coding RNAs microRNAs been found regulate fibrosis through modulation activity related pathways. miR-144-3p, miR-451, miR-200b, miR-328 are among that participate pathology cardiac fibrosis. Meanwhile, miR-34a, miR-17-5p, miR-122, miR-146a, miR-350 liver different situations. PVT1, MALAT1, GAS5, NRON, PFL, MIAT, HULC, ANRIL, H19 We review impact aging-related pathologies.

Language: Английский

Citations

119
The Epithelial-to-Mesenchymal Transition as a Possible Therapeutic Target in Fibrotic Disorders DOI Creative Commons
Jacopo Di Gregorio, Iole Robuffo, Sonia Spalletta

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: Dec. 21, 2020

Fibrosis is a chronic and progressive disorder characterized by excessive deposition of extracellular matrix, which leads to scarring loss function the affected organ or tissue. Indeed, fibrotic process affects variety organs tissues, with specific molecular background. However, two common hallmarks are shared: crucial role transforming growth factor-beta (TGF-β) involvement inflammation process, that essential for initiating degeneration. TGF-β in particular but also other cytokines regulate most mechanism at basis fibrosis, Epithelial-to-Mesenchymal Transition (EMT). EMT has been extensively studied, not yet fully explored as possible therapeutic target fibrosis. A deeper understanding crosstalk between fibrosis may represent an opportunity development broadly effective anti-fibrotic therapy. Here we report evidences relationship multi-organ approaches be developed exploiting this relationship.

Language: Английский

Citations

117
The Roles and Mechanisms of lncRNAs in Liver Fibrosis DOI Open Access
Zhi He, Deying Yang, Xiaolan Fan

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(4), P. 1482 - 1482

Published: Feb. 21, 2020

Many studies have revealed that circulating long noncoding RNAs (lncRNAs) regulate gene and protein expression in the process of hepatic fibrosis. Liver fibrosis is a reversible wound healing response followed by excessive extracellular matrix accumulation. In development liver fibrosis, some lncRNAs diverse cellular processes acting as competing endogenous (ceRNAs) binding proteins. Previous investigations demonstrated overexpression such H19, maternally expressed 3 (MEG3), growth arrest-specific transcript 5 (GAS5), Gm5091, NR_002155.1, HIF 1alpha-antisense RNA 1 (HIF1A-AS1) can inhibit progression Furthermore, upregulation several [e.g., nuclear paraspeckle assembly (NEAT1), hox antisense (Hotair), liver-enriched fibrosis-associated lncRNA1 (lnc-LFAR1)] has been reported to promote This review will focus on functions mechanisms lncRNAs, lncRNA transcriptome profile main involved signalling pathways provides insight into screening therapeutic diagnostic markers

Language: Английский

Citations

102
LncRNA MEG3 functions as a ceRNA in regulating hepatic lipogenesis by competitively binding to miR-21 with LRP6 DOI
Peng Huang, Feizhou Huang,

Huai-Zheng Liu

et al.

Metabolism, Journal Year: 2019, Volume and Issue: 94, P. 1 - 8

Published: Feb. 1, 2019

Language: Английский

Citations

84
Our emerging understanding of the roles of long non-coding RNAs in normal liver function, disease, and malignancy DOI Creative Commons
Amin Mahpour, Alan C. Mullen

JHEP Reports, Journal Year: 2020, Volume and Issue: 3(1), P. 100177 - 100177

Published: Sept. 3, 2020

Long non-coding RNAs (lncRNAs) are important biological mediators that regulate numerous cellular processes. New experimental evidence suggests lncRNAs play essential roles in liver development, normal physiology, fibrosis, and malignancy, including hepatocellular carcinoma cholangiocarcinoma. In this review, we summarise our current understanding of the function both health disease, as well discuss approaches could be used to target these transcripts for therapeutic purposes.

Language: Английский

Citations

63
Regulatory Non-coding RNAs Network in Non-alcoholic Fatty Liver Disease DOI Creative Commons
Siti Aishah Sulaiman, Nor I A Muhsin,

Rahman Jamal

et al.

Frontiers in Physiology, Journal Year: 2019, Volume and Issue: 10

Published: March 19, 2019

Non-alcoholic fatty liver disease (NAFLD) spectrum comprises simple steatosis and non-alcoholic steatohepatitis (NASH) that can lead to fibrosis cirrhosis. The patients usually have no history of excessive alcohol consumption other etiologies cause liver. Understanding the pathophysiology NAFLD has revealed noncoding RNAs (ncRNAs) play significant roles in modulating susceptibility, pathogenesis progression. Currently, ncRNAs are grouped according their sizes regulatory or housekeeping functions. Each these a wide range involvement regulation genes biological pathways. Here, we briefly review current literature progression, mainly microRNAs, long circular RNAs. We also discuss co-regulatory functions interactions between pathogenesis. Elucidation may facilitate identification early diagnostic biomarkers development therapeutic strategies for NAFLD.

Language: Английский

Citations

57
Noncoding RNAs in Nonalcoholic Fatty Liver Disease: Potential Diagnosis and Prognosis Biomarkers DOI Open Access
Olfa Khalifa, Khaoula Errafii‬, Nayla S. Al-Akl

et al.

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

Citations

55
Long noncoding RNA Meg3 sponges miR-708 to inhibit intestinal tumorigenesis via SOCS3-repressed cancer stem cells growth DOI Creative Commons
Shuo Zhang, Weiwei Ji, Wei Wei

et al.

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 13(1)

Published: Dec. 21, 2021

Abstract Background Colorectal cancer (CRC) remains the most common gastrointestinal and a leading cause of deaths worldwide, with showing pathologies indicating malignant transformation early stage intestinal stem cells. The long non-coding RNA Meg3 , which functions as tumor suppressor, has been reported to be abnormal in multiple tumorigenesis events; however, underlying mechanism by contributes proliferation colonic cells unclear. Methods We analyzed expression levels miR-708 SOCS3 samples from Apc loss-of-function ( min ) mice patients CRC, particularly crypt AMO/DSS-induced model (in vivo) organoid culture system vitro) were used explore effect / /SOCS3 axis on colon. In vitro, we performed RNApull-down, immunoprecipitation, luciferase reporter assays using DLD1 RKO cell lines. Findings signaling plays critical role CRC development. Our data showed negatively correlate both clinical mouse model, indicated that acts competitive endogenous (ceRNA) . Then, served an oncogene, inducing neoplasia cultured organoids. Put together, appears promote targeting SOCS3/STAT3 signaling. Interpretation These revealed sponges inhibit development via SOCS3-mediated repression provides potential targets for diagnosis treatment CRC.

Language: Английский

Citations

42
Epigenetic modification in liver fibrosis: Promising therapeutic direction with significant challenges ahead DOI Creative Commons
Runping Liu, Yajing Li, Qi Zheng

et al.

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

Citations

20