The role of miRNAs in liver diseases: Potential therapeutic and clinical applications

Doghish, Ahmed S.; Elballal, Mohammed S.; Elazazy, Ola; Elesawy, Ahmed E.; Elrebehy, Mahmoud A.; Shahin, Reem K.; Midan, Heba M.; Sallam, Al-Aliaa M.

doi:10.1016/j.prp.2023.154375

Cited by 77 publications

(20 citation statements)

References 256 publications

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“…Conversely, the dysregulation of specific miRNAs has been implicated in the development and progression of various CLDs, including non-alcoholic fatty liver disease (NAFLD, e.g., miR-122; [4]), alcoholic liver disease (ALD, e.g., miR-155; [5]), viral hepatitis (e.g., miR-146a; [6]), and HCC (e.g., miR-21; [7]). Overall, miRNAs have undoubtedly emerged as exceptionally promising targets for an extensive array of therapeutic and clinical applications [8]. In this study, we aimed to identify miRNAs associated with non-resolving inflammation by conducting a high-throughput analysis of miRNA expression in HCC models characterized by an inflammatory milieu.…”

Section: Introductionmentioning

confidence: 99%

Differential Modulation of miR-122 Transcription by TGFβ1/BMP6: Implications for Nonresolving Inflammation and Hepatocarcinogenesis

Paluschinski,

Kordes,

Vucur

et al. 2023

Cells

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Chronic inflammation is widely recognized as a significant factor that promotes and worsens the development of malignancies, including hepatocellular carcinoma. This study aimed to explore the potential role of microRNAs in inflammation-associated nonresolving hepatocarcinogenesis. By conducting a comprehensive analysis of altered microRNAs in animal models with liver cancer of various etiologies, we identified miR-122 as the most significantly downregulated microRNA in the liver of animals with inflammation-associated liver cancer. Although previous research has indicated the importance of miR-122 in maintaining hepatocyte function, its specific role as either the trigger or the consequence of underlying diseases remains unclear. Through extensive analysis of animals and in vitro models, we have successfully demonstrated that miR-122 transcription is differentially regulated by the immunoregulatory cytokines, by the transforming growth factor-beta 1 (TGFβ1), and the bone morphogenetic protein-6 (BMP6). Furthermore, we presented convincing evidence directly linking reduced miR-122 transcription to inflammation and in chronic liver diseases. The results of this study strongly suggest that prolonged activation of pro-inflammatory signaling pathways, leading to disruption of cytokine-mediated regulation of miR-122, may significantly contribute to the onset and exacerbation of chronic liver disease.

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Section: Introductionmentioning

confidence: 99%

Differential Modulation of miR-122 Transcription by TGFβ1/BMP6: Implications for Nonresolving Inflammation and Hepatocarcinogenesis

Paluschinski,

Kordes,

Vucur

et al. 2023

Cells

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“…miRNA profiling and technical aspects regarding the isolation procedure of the same is not clearly resolved and lacks internal controls. The miRNA agents fail to attribute their stipulated effect in the in vivo scenario 226 . Furthermore, the drug delivery in miRNA therapy is extremely challenging.…”

Section: Conclusion and Future Outlookmentioning

confidence: 99%

Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review

Nag,

Mitra,

Tripathi

et al. 2023

Immunity Inflam & Disease

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BackgroundAutoimmune diseases (AD) are severe pathophysiological ailments that are stimulated by an exaggerated immunogenic response towards self‐antigens, which can cause systemic or site‐specific organ damage. An array of complex genetic and epigenetic facets majorly contributes to the progression of AD, thus providing significant insight into the regulatory mechanism of microRNA (miRNA). miRNAs are short, non‐coding RNAs that have been identified as essential contributors to the post‐transcriptional regulation of host genome expression and as crucial regulators of a myriad of biological processes such as immune homeostasis, T helper cell differentiation, central and peripheral tolerance, and immune cell development.AimsThis article tends to deliberate and conceptualize the brief pathogenesis and pertinent epigenetic regulatory mechanism as well as miRNA networks majorly affecting five different ADs namely rheumatoid arthritis (RA), type 1 diabetes, multiple sclerosis (MS), systemic lupus erythematosus (SLE) and inflammatory bowel disorder (IBD) thereby providing novel miRNA‐based theranostic interventions.Results & DiscussionPertaining to the differential expression of miRNA attributed in target tissues and cellular bodies of innate and adaptive immunity, a paradigm of scientific expeditions suggests an optimistic correlation between immunogenic dysfunction and miRNA alterations.ConclusionTherefore, it is not astonishing that dysregulations in miRNA expression patterns are now recognized in a wide spectrum of disorders, establishing themselves as potential biomarkers and therapeutic targets. Owing to its theranostic potencies, miRNA targets have been widely utilized in the development of biosensors and other therapeutic molecules originating from the same.

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“… LncRNAs can behave like an oncogene-long noncoding RNA (OncoLncs) [ 14 ] or as a tumor suppressor long noncoding RNA (TSLncs) [ 15 , 16 ]. Non-coding RNAs, such as lncRNAs and miRNAs, are now known to have a role in a wide variety of processes that lead to a wide variety of disorders [ 17 ]. LncRNAs serve as potential diagnostic biomarkers for HCC with high sensitivity and specificity [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

The clinical significance of long non-coding RNAs MALAT1 and CASC2 in the diagnosis of HCV-related hepatocellular carcinoma

Golam,

Khalil,

Shaker

et al. 2024

PLoS ONE

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Background Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. Objective This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. Materials and methods The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. Results The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). Conclusion Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.

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The role of miRNAs in liver diseases: Potential therapeutic and clinical applications

Cited by 77 publications

References 256 publications

Differential Modulation of miR-122 Transcription by TGFβ1/BMP6: Implications for Nonresolving Inflammation and Hepatocarcinogenesis

Differential Modulation of miR-122 Transcription by TGFβ1/BMP6: Implications for Nonresolving Inflammation and Hepatocarcinogenesis

Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review

The clinical significance of long non-coding RNAs MALAT1 and CASC2 in the diagnosis of HCV-related hepatocellular carcinoma

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