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

Khalifa, Olfa; Errafii, Khaoula; Al-Akl, Nayla S.; Arredouani, Abdelilah

doi:10.1155/2020/8822859

Cited by 31 publications

(52 citation statements)

References 134 publications

(158 reference statements)

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“…In our hands too, the HepG2 cells express GLP-1R (data not shown). Although LncRNAs usually do not translate into proteins, they regulate protein-coding genes and related signaling pathways involved in multiple diseases [ 34 ], including NAFLD [ 3 ]. Our data shows that there were differences in LncRNA expression profiles between untreated and steatotic HepG2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, we found 56 and 123 LncRNAs that were respectively upregulated and downregulated in Ex-4-treated steatotic cells relative to steatotic cells. The function of several of the differentially expressed LncRNAs in our study is unknown, while many others are known to be associated with different diseases such as cancer [ 35 ], and a set of them was previously associated with NAFLD [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

“…NAFLD's hallmark is the excessive cytoplasmic lipid accumulation in liver cells not attributed to alcohol consumption, viral infections, or medication [ 2 ]. The NAFLD's pathogenesis and pathophysiology involve intricate interactions between genetic predisposition and environmental risk factors such as obesity, insulin resistance, diabetes mellitus, and dyslipidemia [ 3 ]. NAFLD's global prevalence is about 25%, but it attains 30% in some regions like the Middle East, South America, and South Asia [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4

et al. 2021

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Background and aims The hallmark of non-alcoholic fatty liver disease (NAFLD) is the excessive hepatic lipid accumulation. Currently, no pharmacotherapy exists for NAFLD. However, the glucagon-like peptide-1 receptor agonists have recently emerged as potential therapeutics. Here, we sought to identify the long non-coding RNAs (LncRNAs) associated with the steatosis improvement induced by the GLP-1R agonist Exendin-4 (Ex-4) in vitro. Methods Steatosis was induced in HepG2 cells with oleic acid. The transcriptomic profiling was performed using total RNA extracted from untreated, steatotic, and Ex-4-treated steatotic cells. We validated a subset of differentially expressed LncRNAs with qRT-PCR and identified the most significantly enriched cellular functions associated with the relevant LncRNAs. Results We confirm that Ex-4 improves steatosis in HepG2 cells. We found 379 and 180 differentially expressed LncRNAs between untreated and steatotic cells and between steatotic and Ex-4-treated steatotic cells, respectively. Interestingly, 22 upregulated LncRNAs in steatotic cells became downregulated with Ex-4 exposure, while 50 downregulated LncRNAs in steatotic cells became upregulated in the presence of Ex-4. Although some LncRNAs, such as MALAT1, H19, and NEAT1, were previously associated with NAFLD, the association of others with steatosis and the positive effect of Ex-4 is being reported for the first time. Functional enrichment analysis identified many critical pathways, including fatty acid and pyruvate metabolism, and insulin, PPAR, Wnt, TGF-β, mTOR, VEGF, NOD-like, and Toll-like receptors signaling pathways. Conclusion Our results suggest that LncRNAs may play essential roles in the mechanisms underlying steatosis improvement in response to GLP-1R agonists and warrant further functional studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4

et al. 2021

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“…X-chromosome inactivation (XCI), which refers to the random selection and transcriptional silence of one of two X-chromosomes in females at the early stages of embryonic development, is a unique dosage compensation mechanism in mammals (Waldron, 2016;Bar et al, 2019;Strehle and Guttman, 2020;Yu B. et al, 2020). In most placental mammals, there are two waves of XCI: the imprinted XCI exists in the fertilized embryo and extraembryonic tissues, and the random XCI persists in the inner cell mass (after implantation around embryonic day 5.5), yet humans lack the imprinted XCI and instead have X chromosome dampening (XCD) (Ropers et al, 1978;Harper et al, 1982;Kung et al, 2013;Lee et al, 2013; van Bemmel et al, 2016;Finestra and Gribnau, 2017;Sahakyan et al, 2018).…”

Section: The Role Of Lncrna Xist In X Chromosome Dosage Compensationmentioning

confidence: 99%

Biological Function of Long Non-coding RNA (LncRNA) Xist

Wang

Min

Guo

et al. 2021

Front. Cell Dev. Biol.

139

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Long non-coding RNAs (lncRNAs) regulate gene expression in a variety of ways at epigenetic, chromatin remodeling, transcriptional, and translational levels. Accumulating evidence suggests that lncRNA X-inactive specific transcript (lncRNA Xist) serves as an important regulator of cell growth and development. Despites its original roles in X-chromosome dosage compensation, lncRNA Xist also participates in the development of tumor and other human diseases by functioning as a competing endogenous RNA (ceRNA). In this review, we comprehensively summarized recent progress in understanding the cellular functions of lncRNA Xist in mammalian cells and discussed current knowledge regarding the ceRNA network of lncRNA Xist in various diseases. Long non-coding RNAs (lncRNAs) are transcripts that are more than 200 nt in length and without an apparent protein-coding capacity (Furlan and Rougeulle, 2016; Maduro et al., 2016). These RNAs are believed to be transcribed by the approximately 98–99% non-coding regions of the human genome (Derrien et al., 2012; Fu, 2014; Montalbano et al., 2017; Slack and Chinnaiyan, 2019), as well as a large variety of genomic regions, such as exonic, tronic, and intergenic regions. Hence, lncRNAs are also divided into eight categories: Intergenic lncRNAs, Intronic lncRNAs, Enhancer lncRNAs, Promoter lncRNAs, Natural antisense/sense lncRNAs, Small nucleolar RNA-ended lncRNAs (sno-lncRNAs), Bidirectional lncRNAs, and non-poly(A) lncRNAs (Ma et al., 2013; Devaux et al., 2015; St Laurent et al., 2015; Chen, 2016; Quinn and Chang, 2016; Richard and Eichhorn, 2018; Connerty et al., 2020). A range of evidence has suggested that lncRNAs function as key regulators in crucial cellular functions, including proliferation, differentiation, apoptosis, migration, and invasion, by regulating the expression level of target genes via epigenomic, transcriptional, or post-transcriptional approaches (Cao et al., 2018). Moreover, lncRNAs detected in body fluids were also believed to serve as potential biomarkers for the diagnosis, prognosis, and monitoring of disease progression, and act as novel and potential drug targets for therapeutic exploitation in human disease (Jiang W. et al., 2018; Zhou et al., 2019a). Long non-coding RNA X-inactive specific transcript (lncRNA Xist) are a set of 15,000–20,000 nt sequences localized in the X chromosome inactivation center (XIC) of chromosome Xq13.2 (Brown et al., 1992; Debrand et al., 1998; Kay, 1998; Lee et al., 2013; da Rocha and Heard, 2017; Yang Z. et al., 2018; Brockdorff, 2019). Previous studies have indicated that lncRNA Xist regulate X chromosome inactivation (XCI), resulting in the inheritable silencing of one of the X-chromosomes during female cell development. Also, it serves a vital regulatory function in the whole spectrum of human disease (notably cancer) and can be used as a novel diagnostic and prognostic biomarker and as a potential therapeutic target for human disease in the clinic (Liu et al., 2018b; Deng et al., 2019; Dinescu et al., 2019; Mutzel and Schulz, 2020; Patrat et al., 2020; Wang et al., 2020a). In particular, lncRNA Xist have been demonstrated to be involved in the development of multiple types of tumors including brain tumor, Leukemia, lung cancer, breast cancer, and liver cancer, with the prominent examples outlined in Table 1. It was also believed that lncRNA Xist (Chaligne and Heard, 2014; Yang Z. et al., 2018) contributed to other diseases, such as pulmonary fibrosis, inflammation, neuropathic pain, cardiomyocyte hypertrophy, and osteoarthritis chondrocytes, and more specific details can be found in Table 2. This review summarizes the current knowledge on the regulatory mechanisms of lncRNA Xist on both chromosome dosage compensation and pathogenesis (especially cancer) processes, with a focus on the regulatory network of lncRNA Xist in human disease.

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“…Noncoding RNAs are a group of RNA molecules without protein-coding capacity, involved in chromatin remodeling and in transcriptional and post-transcriptional gene regulation [ 23 ]. Among noncoding RNAs, especially the microRNAs (miRNA) are deregulated in NAFLD, and several studies have shown the association of miRNAs with liver steatosis [ 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease: Focus on New Biomarkers and Lifestyle Interventions

Notarnicola

Osella

Caruso

et al. 2021

IJMS

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Nonalcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome, characterized from pathological changes in lipid and carbohydrate metabolism. Its main characteristics are excessive lipid accumulation and oxidative stress, which create a lipotoxic environment in hepatocytes leading to liver injury. Recently, many studies have focused on the identification of the genetic and epigenetic modifications that also contribute to NAFLD pathogenesis and their prognostic implications. The present review is aimed to discuss on cellular and metabolic alterations associated with NAFLD, which can be helpful to identify new noninvasive biomarkers. The identification of accumulated lipids in the cell membranes, as well as circulating cytokeratins and exosomes, provides new insights in understanding of NAFLD. This review also suggests that lifestyle modifications remain the main prevention and/or treatment for NAFLD.

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

Cited by 31 publications

References 134 publications

Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4

Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4

Biological Function of Long Non-coding RNA (LncRNA) Xist

Nonalcoholic Fatty Liver Disease: Focus on New Biomarkers and Lifestyle Interventions

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