The Role of Long Noncoding RNAs in the Epigenetic Control of Gene Expression

ChemMedChem ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. 505-510 ◽  
Author(s):  
Mariangela Morlando ◽  
Monica Ballarino ◽  
Alessandro Fatica ◽  
Irene Bozzoni
Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2701
Author(s):  
Naiade Calanca ◽  
Cecilie Abildgaard ◽  
Cláudia Aparecida Rainho ◽  
Silvia Regina Rogatto

Comprehensive large-scale sequencing and bioinformatics analyses have uncovered a myriad of cancer-associated long noncoding RNAs (lncRNAs). Aberrant expression of lncRNAs is associated with epigenetic reprogramming during tumor development and progression, mainly due to their ability to interact with DNA, RNA, or proteins to regulate gene expression. LncRNAs participate in the control of gene expression patterns during development and cell differentiation and can be cell and cancer type specific. In this review, we described the potential of lncRNAs for clinical applications in ovarian cancer (OC). OC is a complex and heterogeneous disease characterized by relapse, chemoresistance, and high mortality rates. Despite advances in diagnosis and treatment, no significant improvements in long-term survival were observed in OC patients. A set of lncRNAs was associated with survival and response to therapy in this malignancy. We manually curated databases and used bioinformatics tools to identify lncRNAs implicated in the epigenetic regulation, along with examples of direct interactions between the lncRNAs and proteins of the epigenetic machinery in OC. The resources and mechanisms presented herein can improve the understanding of OC biology and provide the basis for further investigations regarding the selection of novel biomarkers and therapeutic targets.


2018 ◽  
Vol 86 (4) ◽  
pp. 325
Author(s):  
Przemysław Krzysztof Wirstlein ◽  
Paweł P. Jagodziński ◽  
Małgorzata Szczepańska

The causes of endometriosis remain unexplained. Studying the molecular mechanisms at the origin of the lesions leads to conclusions about the important role of the epigenome. This mini-review is a summary of the current state of knowledge about the processes of epigenetic control of gene expression involved in the pathogenesis of endometriosis.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Guangbing Li ◽  
Haohai Zhang ◽  
Xueshuai Wan ◽  
Xiaobo Yang ◽  
Chengpei Zhu ◽  
...  

Long noncoding RNAs (lncRNAs) have been attracting immense research interests. However, only a handful of lncRNAs had been thoroughly characterized. They were involved in fundamental cellular processes including regulation of gene expression at epigenetics as well as tumorogenesis. In this paper, we give a systematic and comprehensive review of existing literature about lncRNA involvement in hepatocellular carcinoma. This review exhibited that lncRNAs played important roles in tumorigenesis and subsequent prognosis and metastasis of hepatocellular carcinoma and elucidated the role of some specific lncRNAs such as MALAT1 and HOTAIR in the pathophysiology of hepatocellular carcinoma and their potential of being therapeutic targets.


2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Viswanathan Rajagopalan ◽  
Emily Schultz ◽  
Youhua Zhang ◽  
Olga Savinova ◽  
Clifford Costello ◽  
...  

Novel mechanisms associated with therapeutically safe thyroid hormone (TH) therapy are emerging. We have shown that oral triiodo-L-thyronine (T3) offers safe cardioprotection in coronary ligation myocardial infarction (MI), ligation ischemia-reperfusion injury, diabetic cardiomyopathy, etc. via restoration of gene expression. However, safe therapeutic effects following atherosclerosis-driven MI and role of long noncoding RNAs (lncRNAs) is unknown. We employed a mouse model of scavenger receptor B1 knockout with hypomorphic apolipoprotein E. Young adult heterozygote littermates served as controls and all mice received high fat (HF) diet for one month. Along with HF diet, a cohort of homozygotes (HypoE) received therapeutic dose of T3 (5.5 μg/kg/d) in drinking water ad libitum. In HypoE mice, Paigen HF diet induced interstitial fibrotic MI with severe hypertrophic (Heart wt./Body wt., HW/BW: control:4.6±0.14; HypoE:12.9±0.75; p<0.0001) heart failure, depressed left ventricular (LV) contractility, increased end-diastolic pressure, myocyte disarray/loss, vacuolization and inflammatory cell infiltration. Aortic root showed atheromatous lipid deposits and median survival time was 26 days. Cholate-free paigen HF diet, used to achieve more gradual transition showed moderate hypertrophy (HW/BW: control:4.9±0.1; HypoE:7.9±0.95; ; p<0.01), decreased LV contractility, increasing atrial effective refractory period with a median survival of 41.5 days. Other changes include decreased serum thyroxine, increased serum cholesterol, significant splenomegaly and alterations in real-time gene expression of numerous cardiac lncRNAs and limited serum lncRNAs involved in inflammatory and immune responses (>2-fold; p<0.05). Oral T3 therapy with cholate-free diet partially restored LV contractility, atrial refractory period and cardiac lncRNAs without significantly affecting serum lncRNAs. These were accompanied by expected feedback inhibition of thyroxine without negatively impacting hypertrophy or heart rate. This is the first study to show a novel role of lncRNAs in TH-mediated cardioprotection. It also demonstrates possibility of safe preventive T3 therapy in a clinically relevant early coronary artery disease model.


2019 ◽  
Vol 2 (1) ◽  
pp. 67-93 ◽  
Author(s):  
Ruediger Hardeland

Melatonin affects chromatin remodeling, thereby activating or silencing specific genes and, presumably, also by modulating circadian-mediated changes in chromatin structure. Melatonin has been shown to exert effects on chromatin under conditions of toxin exposure, treatment with other hormones such as glucocorticoids or leptin, in cancer, and during developmental processes. Most of the documented actions concern histone modifications or their reversal that facilitate or prevent nucleosome eviction. Less information is available on DNA methylation or demethylation at regulatory CpG islands. To date, this has been mainly studied under conditions of early development, occasionally concerning seasonality or shiftwork with light at night. Another emerging field, which is still insufficiently studied, concerns regulation via DNA-interacting noncoding RNAs, in particular, super-enhancer lncRNAs. Although the direct information on actions by melatonin is widely missing, this field promises to become important, as numerous RNAs of this type have been shown to be rhythmically expressed. The circadian aspect of melatonin’s role in chromatin remodeling and control of gene expression deserves future attention. This includes the role of sirtuin 1, which participates in the circadian machinery and apparently mediates several effects of melatonin that are suppressed by sirtuin inhibitors or sirtuin 1 knockdown. 


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