scholarly journals Advances in RNA Epigenetic Modifications in Hepatocellular Carcinoma and Potential Targeted Intervention Strategies

2021 ◽  
Vol 9 ◽  
Author(s):  
Li-Ran Zhu ◽  
Wei-Jian Ni ◽  
Ming Cai ◽  
Wen-Tao Dai ◽  
Hong Zhou
Keyword(s):  
Hepatocellular Carcinoma ◽  
Therapeutic Targets ◽  
Clinical Applications ◽  
Epigenetic Modifications ◽  
Intervention Strategies ◽  
Targeted Intervention ◽  
Rna Modifications ◽  
Specific Targeting ◽  
Posttranscriptional Modifications ◽  
The Impact

The current interventions for hepatocellular carcinoma (HCC) are not satisfactory, and more precise targets and promising strategies need to be explored. Recent research has demonstrated the non-negligible roles of RNA epigenetic modifications such as N6-methyladenosine (m6A) and 5-methylcytosine (m5C) in various cancers, including HCC. However, the specific targeting mechanisms are not well elucidated. In this review, we focus on the occurrence and detailed physiopathological roles of multiple RNA modifications on diverse RNAs closely related to the HCC process. In particular, we highlight fresh insights into the impact mechanisms of these posttranscriptional modifications on the whole progression of HCC. Furthermore, we analyzed the possibilities and significance of these modifications and regulators as potential therapeutic targets in HCC treatment, which provides the foundation for exploring targeted intervention strategies. This review will propel the identification of promising therapeutic targets and novel strategies that can be translated into clinical applications for HCC treatment.

scholarly journals Progress and Prospects of Long Noncoding RNAs (lncRNAs) in Hepatocellular Carcinoma

2015 ◽  
Vol 36 (2) ◽  
pp. 423-434 ◽  
Author(s):  
Chen Li ◽  
Jing Chen ◽  
Kai Zhang ◽  
Bing Feng ◽  
Rui Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Massively Parallel Sequencing ◽  
Noncoding Rnas ◽  
Therapeutic Targets ◽  
Clinical Applications ◽  
Massively Parallel ◽  
Sequencing Technology ◽  
Underlying Mechanisms ◽  
Noninvasive Markers

Hepatocellular carcinoma (HCC) is one of the most frequently occurring cancers with poor prognosis, and novel diagnostic or prognostic biomarkers and therapeutic targets for HCC are urgently required. With the advance of high-resolution microarrays and massively parallel sequencing technology, lncRNAs are suggested to play critical roles in the tumorigenesis and development of human HCC. To date, dysregulation of many HCC-related lncRNAs such as HULC, HOTAIR, MALAT1, and H19 have been identified. From transcriptional “noise” to indispensable elements, lncRNAs may re-write the central dogma. Also, lncRNAs found in body fluids have demonstrated their utility as fluid-based noninvasive markers for clinical use and as therapeutic targets for HCC. Even though several lncRNAs have been characterized, the underlying mechanisms of their contribution to HCC remain unknown, and many important questions about lncRNAs need resolving. A better understanding of the molecular mechanism in HCC-related lncRNAs will provide a rationale for novel effective lncRNA-based targeted therapies. In this review, we highlight the emerging roles of lncRNAs in HCC, and discuss their potential clinical applications as biomarkers for the diagnosis, prognosis, monitoring and treatment of HCC.

scholarly journals Modulation of Bacterial sRNAs Activity by Epigenetic Modifications: Inputs from the Eukaryotic miRNAs

Genes ◽  
2018 ◽  
Vol 10 (1) ◽  
pp. 22 ◽  
Author(s):  
Brice Felden ◽  
David Gilot
Keyword(s):  
Small Rnas ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Epigenetic Modifications ◽  
Micro Rna ◽  
Rna Modifications ◽  
Base Pairing ◽  
Rna Targets ◽  
Living Organisms ◽  
The Impact

Trans-encoded bacterial regulatory RNAs (sRNAs) are functional analogues of eukaryotic microRNAs (miRNAs). These RNA classes act by base-pairing complementarity with their RNA targets to modulate gene expression (transcription, half-life and/or translation). Based on base-pairing, algorithms predict binding and the impact of small RNAs on targeted-RNAs expression and fate. However, other actors are involved such as RNA binding proteins and epigenetic modifications of the targeted and small RNAs. Post-transcriptional base modifications are widespread in all living organisms where they lower undesired RNA folds through conformation adjustments and influence RNA pairing and stability, especially if remodeling their ends. In bacteria, sRNAs possess RNA modifications either internally (methylation, pseudouridinylation) or at their ends. Nicotinamide adenine dinucleotide were detected at 5′-ends, and polyadenylation can occur at 3′-ends. Eukaryotic miRNAs possess N6-methyladenosine (m6A), A editing into I, and non-templated addition of uridines at their 3′-ends. Biological functions and enzymes involved in those sRNA and micro RNA epigenetic modifications, when known, are presented and challenged.

Mechanisms of liver damage in COVID-19

2020 ◽  
Vol 1 (19) ◽  
pp. 39-46
Author(s):  
T. V. Pinchuk ◽  
N. V. Orlova ◽  
T. G. Suranova ◽  
T. I. Bonkalo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Risk Factor ◽  
Liver Disease ◽  
Liver Function ◽  
Liver Damage ◽  
The World ◽  
Coronavirus Infection ◽  
The Impact ◽  
Analyze Data

At the end of 2019, a new coronavirus (SARS-CoV-2) was discovered in China, causing the coronavirus infection COVID-19. The ongoing COVID-19 pandemic poses a major challenge to health systems around the world. There is still little information on how infection affects liver function and the significance of pre-existing liver disease as a risk factor for infection and severe COVID-19. In addition, some drugs used to treat the new coronavirus infection are hepatotoxic. In this article, we analyze data on the impact of COVID-19 on liver function, as well as on the course and outcome of COVID-19 in patients with liver disease, including hepatocellular carcinoma, or those on immunosuppressive therapy after liver transplantation.

Epigenetic Modifications as Therapeutic Targets

2020 ◽  
Vol 21 (11) ◽  
pp. 1046-1046
Author(s):  
Yi-Chao Zheng ◽  
Si-Qi Feng
Keyword(s):  
Therapeutic Targets ◽  
Epigenetic Modifications

Epigenetic Studies in Psychotherapy: A Systematic Review

2020 ◽  
Vol 16 (2) ◽  
pp. 86-92
Author(s):  
Rafael Penadés ◽  
Bárbara Arias ◽  
Mar Fatjó-Vilas ◽  
Laura González-Vallespí ◽  
Clemente García-Rizo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Dna Methylation ◽  
Mental Disorders ◽  
Epigenetic Modifications ◽  
Symptom Improvement ◽  
Epigenetic Changes ◽  
Main Hypothesis ◽  
Psychological Treatments ◽  
Time Period ◽  
The Impact

Background: Epigenetic modifications appear to be dynamic and they might be affected by environmental factors. The possibility of influencing these processes through psychotherapy has been suggested. Objective: To analyse the impact of psychotherapy on epigenetics when applied to mental disorders. The main hypothesis is that psychological treatments will produce epigenetic modifications related to the improvement of treated symptoms. Methods: A computerised and systematic search was completed throughout the time period from 1990 to 2019 on the PubMed, ScienceDirect and Scopus databases. Results: In total, 11 studies were selected. The studies were evaluated for the theoretical framework, genes involved, type of psychotherapy and clinical challenges and perspectives. All studies showed detectable changes at the epigenetic level, like DNA methylation changes, associated with symptom improvement after psychotherapy. Conclusion: Methylation profiles could be moderating treatment effects of psychotherapy. Beyond the detected epigenetic changes after psychotherapy, the epigenetic status before the implementation could act as an effective predictor of response.

scholarly journals The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroaki Kanzaki ◽  
Tetsuhiro Chiba ◽  
Junjie Ao ◽  
Keisuke Koroki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antitumor Effects ◽  
The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

scholarly journals The Impact of Time Interval between Hepatic Resection and Liver Transplantation on Clinical Outcome in Patients with Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2398
Author(s):  
Matteo Serenari ◽  
Enrico Prosperi ◽  
Marc-Antoine Allard ◽  
Michele Paterno ◽  
Nicolas Golse ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Hepatic Resection ◽  
Primary Outcome ◽  
Polynomial Regression ◽  
Secondary Outcome ◽  
Time Interval ◽  
Comprehensive Complication Index ◽  
Fractional Polynomial ◽  
The Impact

Hepatic resection (HR) for hepatocellular carcinoma (HCC) may require secondary liver transplantation (SLT). However, a previous HR is supposed to worsen post-SLT outcomes. Data of patients treated by SLT between 2000 and 2018 at two tertiary referral centers were analyzed. The primary outcome of the study was to analyze the impact of HR on post-LT complications. A Comprehensive Complication Index ≥ 29.6 was chosen as cutoff. The secondary outcome was HCC-related death by means of competing-risk regression analysis. In the study period, 140 patients were included. Patients were transplanted in a median of 23 months after HR (IQR 14–41). Among all the features analyzed regarding the prior HR, only time interval between HR and SLT (time HR-SLT) was an independent predictor of severe complications after LT (OR = 0.98, p < 0.001). According to fractional polynomial regression, the probability of severe complications increased up to 15 months after HR (43%), then slowly decreased over time (OR = 0.88, p < 0.001). There was no significant association between HCC-related death and time HR-SLT at the multivariable competing risks regression model (SHR, 1.06; 95% CI: 0.69–1.62, p = 0.796). This study showed that time HR-SLT was key in predicting complications after LT, without affecting HCC-related death.

CSF extracellular vesicles and risk of disease activity after a first demyelinating event

2021 ◽  
pp. 135245852098754
Author(s):  
Gloria Dalla Costa ◽  
Tommaso Croese ◽  
Marco Pisa ◽  
Annamaria Finardi ◽  
Lorena Fabbella ◽  
...  
Keyword(s):  
Disease Activity ◽  
Extracellular Vesicles ◽  
Prognostic Markers ◽  
Cell Communication ◽  
Extracellular Vesicle ◽  
Intervention Strategies ◽  
Targeted Intervention ◽  
Improve Risk Stratification ◽  
Risk Of Disease ◽  
In Cis

Background: Extracellular vesicles (EVs), a recently described mechanism of cell communication, are released from activated microglial cells and macrophages and are a candidate biomarker in diseases characterized by chronic inflammatory process such as multiple sclerosis (MS). Methods: We explored cerebrospinal fluid extracellular vesicle (CSF EV) of myeloid origin (MEVs), cytokine and chemokine levels in patients with clinically isolated syndrome (CIS). Results: We found that CSF MEVs were significantly higher in CIS patients than in controls and were inversely correlated to CSF CCL2 levels. MEVs level were significantly associated with an shorter time to evidence of disease activity (hazard ratio: 1.01, 95% confidence interval: 1.00–1.02, p < 0.01) independently from other known prognostic markers. Conclusion: After a first demyelinating event, CSF EVs may improve risk stratification of these patients and allow more targeted intervention strategies.

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