Long Noncoding RNA H19: A Key Player in Liver Diseases

Wang, Yanyan; Hylemon, Phillip B.; Zhou, Huiping

doi:10.1002/hep.31765

Cited by 31 publications

(28 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the mRNA levels of Acta2 and Col1a1 were dramatically increased in TGF-β-treated group, which were significantly reduced after FA treatment at medium and high doses ( Figure 4B ). We recently reported that the aberrant expression of long noncoding RNA (lncRNA) H19 was responsible for HSC activation and liver fibrosis progression in multiple mouse models ( Wang et al, 2021 ). As shown in Figure 4B , TGF-β-induced upregulation of H19 was significantly reversed by FA in LX-2 cells.…”

Section: Resultsmentioning

confidence: 99%

Ferulic Acid Ameliorates Hepatic Inflammation and Fibrotic Liver Injury by Inhibiting PTP1B Activity and Subsequent Promoting AMPK Phosphorylation

Xue

Fan

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Chronic inflammation in response to persistent exogenous stimuli or damage results in liver fibrosis, which subsequently progresses into malignant liver diseases with high morbidity and mortality. Ferulic acid (FA) is a phenolic acid widely isolated from abundant plants and exhibits multiple biological activities including anti-oxidant, anti-inflammation and enhancement of immune responses. Adenosine monophosphate-activated protein kinase (AMPK) functions as a critical energy sensor and is regulated through the phosphorylation of liver kinases like LKB1 or dephosphorylation by protein tyrosine phosphatases (PTPs). However, the role of FA in carbon tetrachloride (CCl4)-induced chronic inflammation and liver fibrosis and AMPK activation has not been elucidated. Here we reported that FA ameliorated CCl4-induced inflammation and fibrotic liver damage in mice as indicated by reduced levels of serum liver function enzyme activities and decreased expression of genes and proteins associated with fibrogenesis. Additionally, FA inhibited hepatic oxidative stress, macrophage activation and HSC activation via AMPK phosphorylation in different liver cells. Mechanically, without the participation of LKB1, FA-induced anti-inflammatory and anti-fibrotic effects were abrogated by a specific AMPK inhibitor, compound C. Combining with the results of molecular docking, surface plasmon resonance and co-immunoprecipitation assays, we further demonstrated that FA directly bound to and inhibited PTP1B, an enzyme responsible for dephosphorylating key protein kinases, and eventually leading to the phosphorylation of AMPK. In summary, our results indicated that FA alleviated oxidative stress, hepatic inflammation and fibrotic response in livers through PTP1B-AMPK signaling pathways. Taken together, we provide novel insights into the potential of FA as a natural product-derived therapeutic agent for the treatment of fibrotic liver injury.

show abstract

Section: Resultsmentioning

confidence: 99%

Ferulic Acid Ameliorates Hepatic Inflammation and Fibrotic Liver Injury by Inhibiting PTP1B Activity and Subsequent Promoting AMPK Phosphorylation

Xue

Fan

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…However, further studies are needed to elucidate the role of lncRNA-H19 in non-alcoholic fatty liver (NAFLD) disease progression. 27 Whilst overexpression of lncRNA-H19 has been identified in tissue or plasma of various types of human cancers, including gastric, bladder, breast or pancreatic, 39 its role in HCC remains controversial. 26 In this study, lncRNA-H19 levels were significantly higher in patients with HCC versus cirrhotic patients at no risk of developing HCC (no cancer during follow-up).…”

Section: Discussionmentioning

confidence: 99%

Long non‐coding RNA H19 as a biomarker for hepatocellular carcinoma

Rojas

Gil‐Gómez

Cruz‐Ojeda

et al. 2022

Liver International

View full text Add to dashboard Cite

Background and Aims Liver cancer stem cells (CSCs) could be involved in the carcinogenesis, recurrence, metastasis and chemoresistance of hepatocellular carcinoma (HCC). The aim of this study was to explore the role of lncRNA‐H19 as a biomarker for liver cancer. Methods LncRNA‐H19 expression levels and the functional assays were conducted in EpCAM+CD133+ CSCs and C57BL/6J mice fed with a high‐fat high‐cholesterol carbohydrate (HFHCC) or standard diet for 52 weeks. Liver tissue and plasma samples from patients with cirrhosis, with or without HCC, were used for the analyses of gene expression and circulating lncRNA‐H19 levels in an estimation and validation cohort. Results EpCAM+CD133+ cells showed a stem cell‐like phenotype, self‐renewal capacity, upregulation of pluripotent gene expression and overexpressed lncRNA‐H19 (p < .001). Suppression of lncRNA‐H19 by antisense oligonucleotide treatment significantly reduced the self‐renewal capacity (p < .001). EpCAM, CD133 and lncRNA‐h19 expression increased accordingly with disease progression in HFHCC‐fed mice (p < .05) and also in liver tissue from HCC patients (p = .0082). Circulating lncRNA‐H19 levels were significantly increased in HCC patients in both cohorts (p = .013; p < .0001). In addition, lncRNA‐H19 levels increased accordingly with BCLC staging (p < .0001) and decreased after a partial and complete therapeutic response (p < .05). In addition, patients with cirrhosis who developed HCC during follow‐up showed higher lncRNA‐H19 levels (p = .0025). Conclusion LncRNA‐H19 expression was increased in CSCs, in liver tissue and plasma of patients with HCC and decreased after partial/complete therapeutic response. Those patients who developed HCC during the follow‐up showed higher levels of lncRNA‐H19. LncRNA‐H19 could constitute a new biomarker of HCC.

show abstract

“…LncRNA H19, which is firstly described as a fetal transcript in mice in 1984, is located on chromosome 11p15.5 and expressed exclusively from the maternal allele ( 131 , 132 ). Recent studies indicate that H19 is dysregulated in various cancer types and serves as oncogene or tumor suppressor to affect the development and progression of cancer through various mechanisms.…”

Section: H19/mir-194/pftk1mentioning

confidence: 99%

Long Noncoding Competing Endogenous RNA Networks in Pancreatic Cancer

et al. 2021

View full text Add to dashboard Cite

Pancreatic cancer (PC) is a highly malignant disease characterized by insidious onset, rapid progress, and poor therapeutic effects. The molecular mechanisms associated with PC initiation and progression are largely insufficient, hampering the exploitation of novel diagnostic biomarkers and development of efficient therapeutic strategies. Emerging evidence recently reveals that noncoding RNAs (ncRNAs), including long ncRNAs (lncRNAs) and microRNAs (miRNAs), extensively participate in PC pathogenesis. Specifically, lncRNAs can function as competing endogenous RNAs (ceRNAs), competitively sequestering miRNAs, therefore modulating the expression levels of their downstream target genes. Such complex lncRNA/miRNA/mRNA networks, namely, ceRNA networks, play crucial roles in the biological processes of PC by regulating cell growth and survival, epithelial–mesenchymal transition and metastasis, cancer stem cell maintenance, metabolism, autophagy, chemoresistance, and angiogenesis. In this review, the emerging knowledge on the lncRNA-associated ceRNA networks involved in PC initiation and progression will be summarized, and the potentials of the competitive crosstalk as diagnostic, prognostic, and therapeutic targets will be comprehensively discussed.

show abstract

Long Noncoding RNA H19: A Key Player in Liver Diseases

Abstract: The role of lncRNA H19 in the regulation of liver development has been well documented. (8) Genetic and molecular studies have shown that H19 is a parentally imprinted and maternally expressed gene, which is localized to chromosome 7 in mice and chromosome 11p15.5 in humans, downstream

Cited by 31 publications

References 47 publications

Ferulic Acid Ameliorates Hepatic Inflammation and Fibrotic Liver Injury by Inhibiting PTP1B Activity and Subsequent Promoting AMPK Phosphorylation

Ferulic Acid Ameliorates Hepatic Inflammation and Fibrotic Liver Injury by Inhibiting PTP1B Activity and Subsequent Promoting AMPK Phosphorylation

Long non‐coding RNA H19 as a biomarker for hepatocellular carcinoma

Long Noncoding Competing Endogenous RNA Networks in Pancreatic Cancer

Contact Info

Product

Resources

About