mRNA-miRNA-lncRNA Regulatory Network in Nonalcoholic Fatty Liver Disease

Matboli, Marwa; GadAllah, Shaimaa; Rashed, Wafaa M.; Hasanin, Amany Helmy; Essawy, Nada; Ghanem, Hala M.; Eissa, Sanaa

doi:10.3390/ijms22136770

Cited by 20 publications

(16 citation statements)

References 83 publications

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“…The liver is considered an organ of the innate immune response that filter endogenous signaling molecules and invading pathogens. Accordingly, the presence of multiple insults concomitantly activates the components of innate immunity, thus triggering chronic hepatic inflammation and steatosis, allowing the progression of NAFLD into NASH [ 26 ]. Similarly, NOD-like receptors (NLRs) had been recognized as an important aspect in NASH pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study

et al. 2021

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Background: Non-alcoholic steatohepatitis ((NASH) is the progressive form of (non-alcoholic fatty liver disease) (NAFLD), which can progress to liver cirrhosis and hepatocellular carcinoma. There is no available reliable non-invasive diagnostic tool to diagnose NASH, and still the liver biopsy is the gold standard in diagnosis. In this pilot study, we aimed to evaluate the Nod-like receptor (NLR) signaling pathway related RNA panel in the diagnosis of NASH. Methods: Bioinformatics analysis was done, with retrieval of the HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA panel based on the relation to the NLR-signaling pathway. Hepatitis serum markers, lipid profile, NAFLD score and fibrosis score were assessed in the patients’ sera. Reverse transcriptase real time polymerase chain reaction (RT-PCR) was done to assess the relative expression of the RNA panel among patients who had NAFLD without steatosis, NAFLD with simple steatosis, NASH and healthy controls. Results: We observed up-regulation of Lnc-SPARCL1-1:2 lncRNA that led to upregulation of miR-6881-5P with a subsequent increase in levels of HSPD1, MMP14, and ITGB1 mRNAs. In addition, ROC curve analysis was done, with discriminative cutoff values that aided discrimination between NASH cases and control, and also between NAFLD, simple steatosis and NASH. Conclusion: This pilot study concluded that HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 panel expression has potential in the diagnosis of NASH, and also differentiation between NAFLD, simple steatosis and NASH cases.

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Section: Discussionmentioning

confidence: 99%

Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study

et al. 2021

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“…Long intervening non-coding RNA (lincRNA) is a subclass of non-coding RNA ( 37 ). OLMALINC (LINC00263) and RPARP-AS1 have been identified as important regulators of the pathogenesis of non-alcoholic fatty liver disease ( 38 , 39 ). Studies have shown that OLMALINC (LINC00263), regulated by heterogeneous nuclear ribonucleoprotein K, upregulates CAPN2 through miR-147a, and thus plays an important role in cancer and malignant tumors ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of lncRNAs in the occurrence and development of osteosarcoma

Liu¹,

Zong²,

Sun³

et al. 2022

Transl Pediatr

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Background: Osteosarcoma (OS) is a disease with high mortality in children and adolescents, and metastasis is one of its important clinical features. However, the molecular mechanism of OS occurrence is not completely clear. Thus, we screened potential biomarkers of OS and analyze their prognostic value. Methods:The Cancer Genome Atlas (TCGA) datasets were used to analyze the differential lncRNAs in patients with OS of different immune score and the lncRNAs expressed by immune cells. Cox regression was used to develop the prognosis prediction model and specify the prognosis outcomes. Risk-proportional regression model was constructed, and the samples were divided into high and low groups based on the risk scores for the survival analysis. The areas under the receiver operating characteristic (ROC) curve were calculated and the risk-score model was verified. Finally, using 4 gene sets (comprising chemokines, immune checkpoint blockades, immune activity-related genes, and immune cells), and 4 analysis tools (CIBERSORT, TIMER, XCELL and MCP) to evaluated tumor immune infiltration.Results: Twenty-nine long non-coding ribonucleic acids (lncRNAs) were obtained from the intersection of the screened lncRNAs. Caspase recruitment domain-containing protein 8-antisense RNA 1 (CARD8-AS1), lncRNA five prime to Xist (FTX), KAT8 regulatory NSL complex unit 1-antisense RNA 1 (KANSL1-AS1), Neuroplastin Intronic Transcript 1 (NPTN-IT1), oligodendrocyte maturation-associated long intervening non-coding RNA (OLMALINC) and RPARP Antisense RNA 1 (RPARP-AS1) were found to be correlated with survival. Univariate and multivariate regression analysis showed risk score [HR (hazard ratio) 3.5, P value 0.0043; HR 3.7, P value 0.0033] and metastasis (HR 4.7, P value 6.60E-05; HR 4.8, P value 8.36E-05) were the key factors of patients with OS. The areas under curves (AUCs) of the 1-, 3-, and 5-year ROC curves of the prognostic model were 0.715, 0.729, and 0.771. The low-risk patients tended to have a high abundance of immune cells.Conclusions: This study showed that a risk score based on 6 lncRNAs has potential value in the prognosis of OS, and patients with low-risk scores have high immune cell infiltration and good prognosis. This study may enrich understandings of underlying mechanisms related to the occurrence and development of OS.

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“…Increasing evidence has also highlighted the implicating role of epigenetic mechanisms, including noncoding RNAs (ncRNAs), in the pathogenesis of human NASH [ 10 ]. The main ncRNA classes, long ncRNAs (lncRNAs) and micro RNAs (miRNAs) translate alterations in metabolism and nutrients into a heritable pattern of gene expression [ 11 ]. Moreover, these ncRNAs are playing pivotal roles in inflammation, insulin signaling, and metabolism [ 12 , 13 ] and may facilitate the identification of non-invasive biomarkers or the development of therapeutic strategies for NASH [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, these ncRNAs are playing pivotal roles in inflammation, insulin signaling, and metabolism [ 12 , 13 ] and may facilitate the identification of non-invasive biomarkers or the development of therapeutic strategies for NASH [ 10 ]. Clearly, emerging data also demonstrates the critical role of bioinformatic analysis to identify candidate RNA species as biomarkers for NASH screening, diagnosis, and therapy [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death

Albadawy

Hasanin

Agwa

et al. 2022

IJMS

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Background: Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease that urgently needs effective therapy. Rosavin, a major constituent of the Rhodiola Rosea plant of the family Crassulaceae, is believed to exhibit multiple pharmacological effects on diverse diseases. However, its effect on non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, and the underlying mechanisms are not fully illustrated. Aim: Investigate the pharmacological activity and potential mechanism of rosavin treatment on NASH management via targeting hepatic cell death-related (HSPD1/TNF/MMP14/ITGB1) mRNAs and their upstream noncoding RNA regulators (miRNA-6881-5P and lnc-SPARCL1-1:2) in NASH rats. Results: High sucrose high fat (HSHF) diet-induced NASH rats were treated with different concentrations of rosavin (10, 20, and 30 mg/kg/day) for the last four weeks of dietary manipulation. The data revealed that rosavin had the ability to modulate the expression of the hepatic cell death-related RNA panel through the upregulation of both (HSPD1/TNF/MMP14/ITGB1) mRNAs and their epigenetic regulators (miRNA-6881-5P and lnc-SPARCL1-1:2). Moreover, rosavin ameliorated the deterioration in both liver functions and lipid profile, and thereby improved the hepatic inflammation, fibrosis, and apoptosis, as evidenced by the decreased protein levels of IL6, TNF-α, and caspase-3 in liver sections of treated animals compared to the untreated NASH rats. Conclusion: Rosavin has demonstrated a potential ability to attenuate disease progression and inhibit hepatic cell death in the NASH animal model. The produced effect was correlated with upregulation of the hepatic cell death-related (HSPD1, TNF, MMP14, and ITGB1) mRNAs—(miRNA-6881-5P—(lnc-SPARCL1-1:2) RNA panel.

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mRNA-miRNA-lncRNA Regulatory Network in Nonalcoholic Fatty Liver Disease

Cited by 20 publications

References 83 publications

Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study

Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study

Bioinformatics analysis of lncRNAs in the occurrence and development of osteosarcoma

Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death

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