scholarly journals Remodeling the Epigenetic Landscape of Cancer—Application Potential of Flavonoids in the Prevention and Treatment of Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Weiyi Jiang ◽  
Tingting Xia ◽  
Cun Liu ◽  
Jie Li ◽  
Wenfeng Zhang ◽  
...  

Epigenetics, including DNA methylation, histone modification, and noncoding RNA regulation, are physiological regulatory changes that affect gene expression without modifying the DNA sequence. Although epigenetic disorders are considered a sign of cell carcinogenesis and malignant events that affect tumor progression and drug resistance, in view of the reversible nature of epigenetic modifications, clinicians believe that associated mechanisms can be a key target for cancer prevention and treatment. In contrast, epidemiological and preclinical studies indicated that the epigenome is constantly reprogrammed by intake of natural organic compounds and the environment, suggesting the possibility of utilizing natural compounds to influence epigenetics in cancer therapy. Flavonoids, although not synthesized in the human body, can be consumed daily and are common in medicinal plants, vegetables, fruits, and tea. Recently, numerous reports provided evidence for the regulation of cancer epigenetics by flavonoids. Considering their origin in natural and food sources, few side effects, and remarkable biological activity, the epigenetic antitumor effects of flavonoids warrant further investigation. In this article, we summarized and analyzed the multi-dimensional epigenetic effects of all 6 subtypes of flavonoids (including flavonols, flavones, isoflavones, flavanones, flavanols, and anthocyanidin) in different cancer types. Additionally, our report also provides new insights and a promising direction for future research and development of flavonoids in tumor prevention and treatment via epigenetic modification, in order to realize their potential as cancer therapeutic agents.

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Chao-Chao Yu ◽  
Tao Jiang ◽  
Ao-Fei Yang ◽  
Yan-Jun Du ◽  
Miao Wu ◽  
...  

Tau hyperphosphorylation is a typical pathological change in Alzheimer’s disease (AD) and is involved in the early onset and progression of AD. Epigenetic modification refers to heritable alterations in gene expression that are not caused by direct changes in the DNA sequence of the gene. Epigenetic modifications, such as noncoding RNA regulation, DNA methylation, and histone modification, can directly or indirectly affect the regulation of tau phosphorylation, thereby participating in AD development and progression. This review summarizes the current research progress on the mechanisms of epigenetic modification associated with tau phosphorylation.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guo Huang ◽  
Juan Chen ◽  
Jun Zhou ◽  
Shuai Xiao ◽  
Weihong Zeng ◽  
...  

AbstractThyroid cancer remains the most prevailing endocrine malignancy, and a progressively increasing incidence rate has been observed in recent years, with 95% of thyroid cancer represented by differentiated thyroid carcinomas. The genetics and epigenetics of thyroid cancer are gradually increasing, and gene mutations and methylation changes play an important roles in its occurrence and development. Although the role of RAS and BRAF mutations in thyroid cancer have been partially clarified,but the pathogenesis and molecular mechanisms of thyroid cancer remain to be elucidated. Epigenetic modification refer to genetic modification that does not change the DNA sequence of a gene but causes heritable phenotypic changes in its expression. Epigenetic modification mainly includes four aspects: DNA methylation, chromatin remodelling, noncoding RNA regulation, and histone modification. This article reviews the importance of thyroid cancer epigenetic modification and BRAF gene mutation in the treatment of thyroid cancer.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Eleftheria Hatzimichael ◽  
Tim Crook

Cancer is nowadays considered to be both a genetic and an epigenetic disease. The most well studied epigenetic modification in humans is DNA methylation; however it becomes increasingly acknowledged that DNA methylation does not work alone, but rather is linked to other modifications, such as histone modifications. Epigenetic abnormalities are reversible and as a result novel therapies that work by reversing epigenetic effects are being increasingly explored. The biggest clinical impact of epigenetic modifying agents in neoplastic disorders thus far has been in haematological malignancies, and the efficacy of DNMT inhibitors and HDAC inhibitors in blood cancers clearly attests to the principle that therapeutic modification of the cancer cell epigenome can produce clinical benefit. This paper will discuss the most well studied epigenetic modifications and how these are linked to cancer, will give a brief overview of the clinical use of epigenetics as biomarkers, and will focus in more detail on epigenetic drugs and their use in solid and blood cancers.


2021 ◽  
Vol 15 ◽  
Author(s):  
Jiaqi Zhou ◽  
Miao Li ◽  
Xueying Wang ◽  
Yuwen He ◽  
Yan Xia ◽  
...  

Pharmacotherapy is the most common treatment for schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Pharmacogenetic studies have achieved results with limited clinical utility. DNA methylation (DNAm), an epigenetic modification, has been proposed to be involved in both the pathology and drug treatment of these disorders. Emerging data indicates that DNAm could be used as a predictor of drug response for psychiatric disorders. In this study, we performed a systematic review to evaluate the reproducibility of published changes of drug response-related DNAm in SCZ, BD and MDD. A total of 37 publications were included. Since the studies involved patients of different treatment stages, we partitioned them into three groups based on their primary focuses: (1) medication-induced DNAm changes (n = 8); (2) the relationship between DNAm and clinical improvement (n = 24); and (3) comparison of DNAm status across different medications (n = 14). We found that only BDNF was consistent with the DNAm changes detected in four independent studies for MDD. It was positively correlated with clinical improvement in MDD. To develop better predictive DNAm factors for drug response, we also discussed future research strategies, including experimental, analytical procedures and statistical criteria. Our review shows promising possibilities for using BDNF DNAm as a predictor of antidepressant treatment response for MDD, while more pharmacoepigenetic studies are needed for treatments of various diseases. Future research should take advantage of a system-wide analysis with a strict and standard analytical procedure.


2021 ◽  
Author(s):  
Xuyang Lv ◽  
Jiangchuan Sun ◽  
Linfeng Hu ◽  
Ying Qian ◽  
Chunlei Fan ◽  
...  

Abstract Background: Although curcumol has been shown to possess antitumor effects in several cancers, its effects on glioma are largely unknown. Recently, lncRNAs have been reported to play an oncogenic role through epigenetic modifications. Therefore, here, we investigated whether curcumol inhibited glioma progression by reducing FOXD2-AS1-mediated enhancer of zeste homolog 2 (EZH2) activation.Methods: MTT, colony formation, flow cytometry, Transwell, and neurosphere formation assays were used to assess cell proliferation, cell cycle, apoptosis, the percentage of CD133+ cells, the migration and invasion abilities, and the self-renewal ability. qRT-PCR, western blotting, immunofluorescence, and immunohistochemical staining were used to detect mRNA and protein levels. Isobologram analysis and methylation-specific PCR were used to analyze the effects of curcumol on TMZ resistance in glioma cells. DNA pull-down and Chip assays were employed to explore the molecular mechanism underlying the functions of curcumol in glioma cells. Tumorigenicity was determined using a xenograft formation assay. Results: Curcumol inhibited the proliferation, metastasis, self-renewal ability, and TMZ resistance of glioma cells in vitro and in vivo. FOXD2-AS1 was highly expressed in glioma cell lines, and its expression was suppressed by curcumol treatment in a dose- and time-dependent manner. The forced expression of FOXD2-AS1 abrogated the effect of curcumol on glioma cell proliferation, metastasis, self-renewal ability, and TMZ resistance. Moreover, the forced expression of FOXD2-AS1 reversed the inhibitory effect of curcumol on EZH2 activation.Conclusions: We showed for the first time that curcumol is effective in inhibiting malignant biological behaviors and TMZ-resistance of glioma cells by suppressing FOXD2-AS1-mediated EZH2 activation on anti-oncogenes. Our findings offer the possibility of exploiting curcumol as a promising therapeutic agent for glioma treatment and may provide an option for the clinical application of this natural herbal medicine.


2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Qianyun Feng ◽  
Sheng Zheng ◽  
Jia Zheng

Osteoporosis, a common and multifactorial disease, is influenced by genetic factors and environments. However, the pathogenesis of osteoporosis has not been fully elucidated yet. Recently, emerging evidence suggests that epigenetic modifications may be the underlying mechanisms that link genetic and environmental factors with increased risks of osteoporosis and bone fracture. MicroRNA (miRNA), a major category of small noncoding RNA with 20–22 bases in length, is recognized as one important epigenetic modification. It can mediate post-transcriptional regulation of target genes with cell differentiation and apoptosis. In this review, we aimed to profile the role of miRNA in bone remodeling and its therapeutic implications for osteoporosis. A deeper insight into the role of miRNA in bone remodeling and osteoporosis can provide unique opportunities to develop a novel diagnostic and therapeutic approach of osteoporosis.


2020 ◽  
Vol 10 (5) ◽  
pp. 1211-1220
Author(s):  
Kimberly M Nelson ◽  
Nicholas S Perry ◽  
Keith J Horvath ◽  
Laramie R Smith

Abstract The use of mobile health (mHealth) technologies addressing HIV disparities among gay, bisexual, and other men who have sex with men (GBMSM) has increased. A systematic review of mHealth interventions for HIV prevention and treatment among GBMSM was conducted to summarize the current evidence and provide recommendations for future research. PRISMA guidelines were followed (PROSPERO ID: 148452). Studies identified via PubMed, PsychInfo, or Embase were included that (i) were in English, (ii) were published in a peer-reviewed journal prior to July 1, 2019, (iii) presented primary results, (iv) included only GBMSM, and (v) reported the results of an mHealth intervention (e.g., text message, phone/mobile application [app]) to improve HIV prevention or treatment outcomes. Of 1,636 identified abstracts, 16 published studies met inclusion criteria. Eleven studies were conducted in the United States. One study was a fully powered randomized controlled trial (RCT), seven were single-arm pilots with pre–post assessments, four were pilot RCTs, and four tested public health campaigns with post-assessments. Seven developed study-specific apps, five used text messaging, and four used existing social networking apps. Most (81%) targeted prevention outcomes. Nine cited a specific behavioral theory. All studies found that a mHealth approach was feasible and acceptable. All interventions provided evidence of preliminary efficacy or promising trends on primary outcomes. Although mHealth interventions for HIV prevention and treatment appear feasible and acceptable, most published studies are small pilot trials. Additional research assessing the efficacy and mechanisms of mHealth interventions is needed.


2018 ◽  
Vol 62 (11-12) ◽  
pp. 693-704 ◽  
Author(s):  
Ana Casaca ◽  
Gabriel M. Hauswirth ◽  
Heidi Bildsoe ◽  
Moisés Mallo ◽  
Edwina McGlinn

Precise regulation of Hox gene activity is essential to achieve proper control of animal embryonic development and to avoid generation of a variety of malignancies. This is a multilayered process, including complex polycistronic transcription, RNA processing, microRNA repression, long noncoding RNA regulation and sequence-specific translational control, acting together to achieve robust quantitative and qualitative Hox protein output. For many such mechanisms, the Hox cluster gene network has turned out to serve as a paradigmatic model for their study. In this review, we discuss current knowledge of how the different layers of post-transcriptional regulation and the production of a variety of noncoding RNA species control Hox output, and how this shapes formation of developmental systems that are reproducibly patterned by complex Hox networks.


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