Regulatory Mechanisms of Epigenetic miRNA Relationships in Human Cancer and Potential as Therapeutic Targets

Arif, Kiran; Elliott, Esther K; Haupt, Larisa M.; Griffiths, Lyn R.

doi:10.3390/cancers12102922

Cited by 105 publications

(80 citation statements)

References 184 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Normal miRNA expression and function can be deregulated in cancer [ 11 , 12 ]. Their critical roles in cancer find evidence in a complex map of interactions underlying the relationship between miRNA regulation and the hallmarks of cancer [ 13 ]. A single miRNA can target multiple mRNAs and one mRNA can also be targeted by multiple miRNAs [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

A “Lymphocyte MicroRNA Signature” as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming

Incorvaia

Fanale

Badalamenti

et al. 2020

Cancers

View full text Add to dashboard Cite

Introduction of checkpoint inhibitors resulted in durable responses and improvements in overall survival in advanced RCC patients, but the treatment efficacy is widely variable, and a considerable number of patients are resistant to PD-1/PD-L1 inhibition. This variability of clinical response makes necessary the discovery of predictive biomarkers for patient selection. Previous findings showed that the epigenetic modifications, including an extensive microRNA-mediated regulation of tumor suppressor genes, are key features of RCC. Based on this biological background, we hypothesized that a miRNA expression profile directly identified in the peripheral lymphocytes of the patients before and after the nivolumab administration could represent a step toward a real-time monitoring of the dynamic changes during cancer evolution and treatment. Interestingly, we found a specific subset of miRNAs, called “lymphocyte miRNA signature”, specifically induced in long-responder patients (CR, PR, or SD to nivolumab >18 months). Focusing on the clinical translational potential of miRNAs in controlling the expression of immune checkpoints, we identified the association between the plasma levels of soluble PD-1/PD-L1 and expression of some lymphocyte miRNAs. These findings could help the development of novel dynamic predictive biomarkers urgently needed to predict the potential response to immunotherapy and to guide clinical decision-making in RCC patients.

show abstract

Section: Introductionmentioning

confidence: 99%

A “Lymphocyte MicroRNA Signature” as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming

Incorvaia

Fanale

Badalamenti

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…These four miRNA are all HBx epigenetically dysregulated in various HBV-HCC pathways, as well as exercise diverse roles in both the innate and adaptive immune pathways. In many cases, the same miRNA plays a significant regulatory role in many other cancers like those of the breast, lung and colon ( 147 ). It is important to highlight that the illustrated hypothetical pathways in Figures 2 – 5 occur in a dynamic context and that the degree of influence of any single path is non constant.…”

Section: Hbx-dysregulated Mirna In Hbv-hcc Pathwaysmentioning

confidence: 99%

Section: Hbx-dysregulated Mirna In Hbv-hcc Pathwaysmentioning

confidence: 99%

“…In HBV-HCC and many other cancers, the tumor suppressor miR-101 is regarded as a key miRNA in epigenetic systems ( 147 ) (see Figure 2 ). This HBx-dysregulated miRNA involves both upstream and downstream epigenetic systems and has been widely reported as downregulated in HBV-HCC ( 147 ). The HBx protein can recruit the Polycomb protein EZH2 ( 148 ) to downregulate miR-101 but a feedback loop exists because this miRNA also targets EZH2 ( 149 ).…”

Section: Hbx-dysregulated Mirna In Hbv-hcc Pathwaysmentioning

confidence: 99%

See 1 more Smart Citation

The Epigenetic Modulation of Cancer and Immune Pathways in Hepatitis B Virus-Associated Hepatocellular Carcinoma: The Influence of HBx and miRNA Dysregulation

Sartorius

Winkler

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC) pathogenesis is fueled by persistent HBV infection that stealthily maintains a delicate balance between viral replication and evasion of the host immune system. HBV is remarkably adept at using a combination of both its own, as well as host machinery to ensure its own replication and survival. A key tool in its arsenal, is the HBx protein which can manipulate the epigenetic landscape to decrease its own viral load and enhance persistence, as well as manage host genome epigenetic responses to the presence of viral infection. The HBx protein can initiate epigenetic modifications to dysregulate miRNA expression which, in turn, can regulate downstream epigenetic changes in HBV-HCC pathogenesis. We attempt to link the HBx and miRNA induced epigenetic modulations that influence both the HBV and host genome expression in HBV-HCC pathogenesis. In particular, the review investigates the interplay between CHB infection, the silencing role of miRNA, epigenetic change, immune system expression and HBV-HCC pathogenesis. The review demonstrates exactly how HBx-dysregulated miRNA in HBV-HCC pathogenesis influence and are influenced by epigenetic changes to modulate both viral and host genome expression. In particular, the review identifies a specific subset of HBx induced epigenetic miRNA pathways in HBV-HCC pathogenesis demonstrating the complex interplay between HBV infection, epigenetic change, disease and immune response. The wide-ranging influence of epigenetic change and miRNA modulation offers considerable potential as a therapeutic option in HBV-HCC.

show abstract

“…miRNAs may participate in the epigenetic silencing of genes by DNA methylation, either indirectly through binding to mRNAs encoding transcription factors or by directly affecting the mRNAs coding for DNA methyltransferases [ 13 ]. In turn, the activity of promoters of some miRNAs depends on the expression level of DNA methyltransferases, which form regulatory feedback loops [ 14 ]. According to the base miRWalk, miRanda, RNA22, and Targetscan, one miRNA molecule regulates the expression level of tens to hundreds of genes, and at the same time, one gene is a target for many miRNAs.…”

Section: Introductionmentioning

confidence: 99%

Clusterin and Its Potential Regulatory microRNAs as a Part of Secretome for the Diagnosis of Abnormally Invasive Placenta: Accreta, Increta, and Percreta Cases

Timofeeva

Fedorov

Pirogova

et al. 2021

Life

View full text Add to dashboard Cite

Magnetic resonance imaging (MRI) and ultrasound methods used for the diagnosis of an abnormally invasive placenta (AIP) have a wide range of sensitivity (Se, 33–93%) and specificity (Sp, 71–100%) levels, which results in a high risk of unfavorable maternal and perinatal outcomes. The relevance of optimizing the diagnosis of AIP is beyond doubt. Given the epigenetic nature of trophoblast invasion, we aimed to quantitate microRNAs and proteins of their target genes that are potentially associated with AIP in blood plasma samples from 64 pregnant women at gestation weeks 30–34 by reverse transcription coupled with polymerase chain reaction (RT-PCR) and Western blotting, respectively. Statistically significant increases in the expression levels of hsa-miR-17-5p, hsa-miR-21-5p, hsa-miR-25-3p, hsa-miR-92a-3p, and hsa-miR-320a-3p were revealed in the groups of women with AIP (accreta, increta, percreta) relative to the group of women with scars on the uterus or to the group with placenta previa. Opposite changes in the expression level of “gene–target protein/miRNA” pairs were found for the α-subunit of the clusterin secretory form and any of the hsa-miR-21-5p, hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-320a-3p, and hsa-miR-17-5p in all cases of AIP. The developed logistic regression models to diagnose AIP cases of various severity gave Se values of 88.8–100% and Sp values of 91.6–100% using a combination of hsa-miR-21-5p, hsa-miR-92a-3p, hsa-miR-320a-3p, or clusterin levels.

show abstract

Regulatory Mechanisms of Epigenetic miRNA Relationships in Human Cancer and Potential as Therapeutic Targets

Cited by 105 publications

References 184 publications

A “Lymphocyte MicroRNA Signature” as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming

A “Lymphocyte MicroRNA Signature” as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming

The Epigenetic Modulation of Cancer and Immune Pathways in Hepatitis B Virus-Associated Hepatocellular Carcinoma: The Influence of HBx and miRNA Dysregulation

Clusterin and Its Potential Regulatory microRNAs as a Part of Secretome for the Diagnosis of Abnormally Invasive Placenta: Accreta, Increta, and Percreta Cases

Contact Info

Product

Resources

About