scholarly journals Epigenetic modification and BRAF gene mutation in thyroid carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guo Huang ◽  
Juan Chen ◽  
Jun Zhou ◽  
Shuai Xiao ◽  
Weihong Zeng ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Gene Mutation ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Epigenetic Modification ◽  
Gene Mutations ◽  
Braf Gene ◽  
Braf Mutations ◽  
Rna Regulation

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.

scholarly journals Identification of a novel BRAF Thr599dup mutation in lung adenocarcinoma

Open Medicine ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. 278-280 ◽  
Author(s):  
Xuefei Zhang ◽  
Mo Li ◽  
Desheng Lv ◽  
Ge Sun ◽  
Yu Bai ◽  
...  
Keyword(s):  
Amino Acid ◽  
Gene Mutation ◽  
Clinical Care ◽  
Gene Mutations ◽  
Braf V600e ◽  
Molecular Characteristics ◽  
Braf Gene ◽  
Braf Mutations ◽  
Braf Inhibition ◽  
Next Generation Sequencing Ngs

AbstractBRAF mutations are known as oncogenic drivers of non-small cell lung cancer (NSCLC). BRAF inhibition has demonstrated anti-tumor activity in patients with BRAF V600E mutant NSCLC. Further molecular screening for novel BRAF thr599dup mutation is warranted. The novel BRAF Thr599dup gene mutation, for which the repeat amino acid-tyrosine is inserted between the 599th amino acid and the 600th amino acid in exon 15 of BRAF, was identified by next-generation sequencing (NGS) during routine clinical care in a lung carcinoma sample from an Asian never-smoker. Other putative driver alterations including EGFR, ALK were not found in that patient. BRAF Thr599dup gene mutation analysis was consistent with BRAF v600E gene mutation. Here we report a novel BRAF gene mutation with molecular characteristics consistent with those in BRAF-driven NSCLC. Our case expands the scope of BRAF gene mutations and provides broader molecular profiling for optimizing therapeutic options for patients with NSCLC. The new BRAF gene mutation has important clinical meaning for cancer patients.

scholarly journals Role of Main RNA Methylation in Hepatocellular Carcinoma: N6-Methyladenosine, 5-Methylcytosine, and N1-Methyladenosine

2021 ◽  
Vol 9 ◽  
Author(s):  
Yating Xu ◽  
Menggang Zhang ◽  
Qiyao Zhang ◽  
Xiao Yu ◽  
Zongzong Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cellular Differentiation ◽  
Molecular Mechanisms ◽  
Gene Sequence ◽  
Epigenetic Modification ◽  
Biological Processes ◽  
Biological Functions ◽  
Rna Detection ◽  
Rna Methylation

RNA methylation is considered a significant epigenetic modification, a process that does not alter gene sequence but may play a necessary role in multiple biological processes, such as gene expression, genome editing, and cellular differentiation. With advances in RNA detection, various forms of RNA methylation can be found, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), and 5-methylcytosine (m5C). Emerging reports confirm that dysregulation of RNA methylation gives rise to a variety of human diseases, particularly hepatocellular carcinoma. We will summarize essential regulators of RNA methylation and biological functions of these modifications in coding and noncoding RNAs. In conclusion, we highlight complex molecular mechanisms of m6A, m5C, and m1A associated with hepatocellular carcinoma and hope this review might provide therapeutic potent of RNA methylation to clinical research.

scholarly journals The emerging role of microRNAs in bone remodeling and its therapeutic implications for osteoporosis

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Qianyun Feng ◽  
Sheng Zheng ◽  
Jia Zheng
Keyword(s):  
Bone Remodeling ◽  
Noncoding Rna ◽  
Target Genes ◽  
Epigenetic Modification ◽  
Therapeutic Implications ◽  
Small Noncoding Rna ◽  
Genetic And Environmental Factors ◽  
Underlying Mechanisms ◽  
Post Transcriptional Regulation

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.

Whole Tumor Capsule is Prognostic of a Very Good Outcome in the Classical Variant of Papillary Thyroid Cancer

2021 ◽  
Author(s):  
Carlotta Giani ◽  
Liborio Torregrossa ◽  
Ramone Teresa ◽  
Romei Cristina ◽  
Antonio Matrone ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Braf V600e ◽  
Braf Mutations ◽  
Biological Behaviour ◽  
Non Invasive ◽  
Good Outcome ◽  
Predictive Role ◽  
Pathological Behavior

Abstract Context Tumour capsule integrity is becoming a relevant issue to predict the biological behaviour of human tumours, including thyroid cancer. Aim To verify if a whole tumour capsule in the classical variant of PTC (CVPTC) could have a predictive role of a good outcome as for follicular variant (FVPTC). Methods FVPTC (n=600) and CVPTC (n=554) cases, were analysed. We distinguished encapsulated-FVPTC (E-FVPTC) and encapsulated-CVPTC (E-CVPTC) and, thereafter, invasive (Ei-FVPTC and Ei-CVPTC) and non-invasive (En-FVPTC and En-CVPTC) tumours, according to the invasion or integrity of tumour capsule, respectively. Cases without tumour capsule were indicated as invasive-FVPTC (I-FVPTC) and invasive-CVPTC (I-CVPTC). Sub-group of each variant was evaluated for BRAF mutations. Results E-FVPTC was more frequent than E-CVPTC (p<0.0001). No differences were found between En-FVPTC and En-CVPTC or between Ei-FVPTC and Ei-CVPTC. After 18 years of follow-up, a greater number of not-cured cases were observed in Ei-CVPTC with respect to Ei-FVPTC, but not in En-CVPTC to En-FVPTC. Multivariate clustering analysis showed that En-FVPTC, En-CVPTC, and Ei-FVPTC have similar features but different from I-FVPTC and I-CVPTC and, to a lesser extent, from Ei-CVPTC. 177/614 (28.8%) cases were BRAF  V600E-mutated and 10/614(1.6%) carried BRAF-rare alterations. Significantly higher rate of En-CVPTC (22/49,44.9%) than En-FVPTC (15/195,7.7%) (p<0.0001) were BRAF  V600E-mutated. Conclusions En-CVPTC is less prevalent than En-FVPTC. However, they have a good clinical/ pathological behavior comparable to En-FVPTC. This finding confirms the good prognostic role of a whole tumour capsule also in CVPTC. New nomenclature for En-CVPTC, similar to that introduced for En-FVPTC (i.e, NIFTP) could be envisaged.

scholarly journals Long-Noncoding RNA (lncRNA) in the Regulation of Hypoxia-Inducible Factor (HIF) in Cancer

2020 ◽  
Vol 6 (3) ◽  
pp. 27 ◽  
Author(s):  
Dominik A. Barth ◽  
Felix Prinz ◽  
Julia Teppan ◽  
Katharina Jonas ◽  
Christiane Klec ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Protein Coding ◽  
Rna Molecules ◽  
Von Hippel Lindau ◽  
Hypoxic Conditions ◽  
Main Regulator ◽  
Upstream Regulators

Hypoxia is dangerous for oxygen-dependent cells, therefore, physiological adaption to cellular hypoxic conditions is essential. The transcription factor hypoxia-inducible factor (HIF) is the main regulator of hypoxic metabolic adaption reducing oxygen consumption and is regulated by gradual von Hippel-Lindau (VHL)-dependent proteasomal degradation. Beyond physiology, hypoxia is frequently encountered within solid tumors and first drugs are in clinical trials to tackle this pathway in cancer. Besides hypoxia, cancer cells may promote HIF expression under normoxic conditions by altering various upstream regulators, cumulating in HIF upregulation and enhanced glycolysis and angiogenesis, altogether promoting tumor proliferation and progression. Therefore, understanding the underlying molecular mechanisms is crucial to discover potential future therapeutic targets to evolve cancer therapy. Long non-coding RNAs (lncRNA) are a class of non-protein coding RNA molecules with a length of over 200 nucleotides. They participate in cancer development and progression and might act as either oncogenic or tumor suppressive factors. Additionally, a growing body of evidence supports the role of lncRNAs in the hypoxic and normoxic regulation of HIF and its subunits HIF-1α and HIF-2α in cancer. This review provides a comprehensive update and overview of lncRNAs as regulators of HIFs expression and activation and discusses and highlights potential involved pathways.

scholarly journals Identification of Long Noncoding RNA Associated ceRNA Networks in Rosacea

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Lian Wang ◽  
Ruifeng Lu ◽  
Yujia Wang ◽  
Xiaoyun Wang ◽  
Dan Hao ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Control Group ◽  
Group 13 ◽  
Regulatory Processes ◽  
Coexpression Networks

Rosacea is a chronic and relapsing inflammatory cutaneous disorder with highly variable prevalence worldwide that adversely affects the health of patients and their quality of life. However, the molecular characterization of each rosacea subtype is still unclear. Furthermore, little is known about the role of long noncoding RNAs (lncRNAs) in the pathogenesis or regulatory processes of this disorder. In the current study, we established lncRNA-mRNA coexpression networks for three rosacea subtypes (erythematotelangiectatic, papulopustular, and phymatous) and performed their functional enrichment analyses using Gene Onotology, KEGG, GSEA, and WGCNA. Compared to the control group, 13 differentially expressed lncRNAs and 525 differentially expressed mRNAs were identified in the three rosacea subtypes. The differentially expressed genes identified were enriched in four signaling pathways and the GO terms found were associated with leukocyte migration. In addition, we found nine differentially expressed lncRNAs in all three rosacea subtype-related networks, including NEAT1 and HOTAIR, which may play important roles in the pathology of rosacea. Our study provided novel insights into lncRNA-mRNA coexpression networks to discover the molecular mechanisms involved in rosacea development that can be used as future targets of rosacea diagnosis, prevention, and treatment.

scholarly journals The Mouse Xist Gene: a Model for Studying the Gametic Imprinting Phenomenon

1996 ◽  
Vol 45 (1-2) ◽  
pp. 199-204 ◽  
Author(s):  
M. Zuccotti ◽  
M. Monk
Keyword(s):  
Molecular Mechanisms ◽  
Epigenetic Modification ◽  
Somatic Tissue ◽  
Paternal Allele ◽  
The Status ◽  
Intron Region ◽  
Exon 11 ◽  
Region 10 ◽  
Gametic Imprinting

In mammals, normal embryonic development requires differential genomic imprinting of male and female gametes [1, 2]. Many investigations have been directed towards the understanding of the molecular mechanisms of imprinting and the timing of establishment of the imprint during gametogenesis and its erasure during development.Methylation is the focus of many of these studies as it has been known for some time that this epigenetic modification of the DNA correlates with the status of gene activity. So far, five imprinted genes, expressed from only one of the parental alleles, have been found to be differentially methylated in somatic tissue: mouse Igf2 [3] and Xist [4] and human SNRPN [5, 6] expressed from the paternal allele; mouse Igf2r [7] and H19 [8, 9] expressed from the maternal allele. However, so far, a gametic methylation imprint has been detected for only two of these genes: in an intron region of mouse Igf2r [7], and in the promoter region [10] and the first exon [11] of the Xist (X-inactivation-specific transcript [12, 13] gene.The data accumulated for the Xist gene, during different phases of gametogenesis and development, provides the most comprehensive story about the role of methylation as a primary gametic imprint, and on the timing of its establishment during gametogenesis and erasure during development. Methylation studies have now been performed during oogenesis and spermatogenesis [Norris et al., 1994; 11] and in mature gametes and during early stages of development [10, 11]. In addition, expression of the gene has been described during gametogenesis [14-16] and throughout early development [4-17].

WNK4 enhances TRPV5-mediated calcium transport: potential role in hypercalciuria of familial hyperkalemic hypertension caused by gene mutation of WNK4

2007 ◽  
Vol 292 (2) ◽  
pp. F545-F554 ◽  
Author(s):  
Yi Jiang ◽  
William B. Ferguson ◽  
Ji-Bin Peng
Keyword(s):  
Gene Mutation ◽  
Gene Mutations ◽  
Distal Tubule ◽  
Surface Expression ◽  
Inhibitory Effect ◽  
Xenopus Laevis Oocytes ◽  
Dependent Manner ◽  
Serine Threonine Kinase ◽  
Familial Hyperkalemic Hypertension

The epithelial Ca2+ channel TRPV5 serves as a gatekeeper for active Ca2+ reabsorption in the distal convoluted tubule and connecting tubule of the kidney. WNK4, a protein serine/threonine kinase with gene mutations that cause familial hyperkalemic hypertension (FHH), including a subtype with hypercalciuria, is also localized in the distal tubule of the nephron. To understand the role of WNK4 in modulation of Ca2+ reabsorption, we evaluated the effect of WNK4 on TRPV5-mediated Ca2+ transport in Xenopus laevis oocytes. Coexpression of TRPV5 with WNK4 resulted in a twofold increase in TRPV5-mediated Ca2+ uptake. The increase in Ca2+ uptake was due to the increase in surface expression of TRPV5. When the thiazide-sensitive Na+-Cl− cotransporter NCC was coexpressed, the effect of WNK4 on TRPV5 was weakened by NCC in a dose-dependent manner. Although the WNK4 disease-causing mutants E562K, D564A, Q565E, and R1185C retained their ability to upregulate TRPV5, the blocking effect of NCC was further strengthened when wild-type WNK4 was replaced by the Q565E mutant, which causes FHH with hypercalciuria. We conclude that WNK4 positively regulates TRPV5-mediated Ca2+ transport and that the inhibitory effect of NCC on this process may be involved in the pathogenesis of hypercalciuria of FHH caused by gene mutation in WNK4.

The role of the zinc transporter SLC30A2/ZnT2 in transient neonatal zinc deficiency

Metallomics ◽  
2017 ◽  
Vol 9 (10) ◽  
pp. 1352-1366 ◽  
Author(s):  
Yarden Golan ◽  
Taiho Kambe ◽  
Yehuda G. Assaraf
Keyword(s):  
Zinc Deficiency ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Gene Mutations ◽  
Zinc Transporter ◽  
Loss Of Function ◽  
Breastfed Infants ◽  
Nursing Mothers ◽  
Novel Approaches

Transient neonatal zinc deficiency (TNZD) results from loss of function mutations in theSLC30A2/ZnT2gene. Nursing mothers harboring this defective zinc transporter produce zinc-deficient milk. Consequently, their exclusively breastfed infants develop severe zinc deficiency. The present review summarizes our current knowledge onSLC30A2/ZnT2gene mutations and highlights the molecular mechanisms underlying this zinc deficiency. We further propose novel approaches for the early diagnosis and prevention of TNZD.

scholarly journals Modern concepts of the molecular pathogenesis of thyroid cancer

2021 ◽  
Vol 8 (2) ◽  
pp. 8-22
Author(s):  
A. A. Mikhailova ◽  
A. V. Shestakov ◽  
K. A. Chubakova ◽  
E. V. Kolokolova ◽  
V. Yu. Eliseev ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Markers ◽  
Molecular Mechanisms ◽  
Thyroid Nodules ◽  
Gene Mutations ◽  
Endocrine System ◽  
Nodular Goiter ◽  
Micro Rna ◽  
Diagnostic Methods ◽  
Patient Treatment

Thyroid cancer remains the most common malignancy of the endocrine system worldwide. The indicators of its morbidity and mortality rates have been increasing rapidly over the last decades. Most cases of differentiated thyroid cancer (follicular and papillary histotypes) are clinically manifested by nodular goiter frequently combined with uncertain results of cytological diagnosis (categories III and IV according to the Bethesda (Bethesda System for Reporting Thyroid Cytopathology) classification). All of that makes it difficult to choose a proper tactic for patient treatment. It is known that the development, progression, invasion, and metastasis of cancer cells are regulated by a variety of molecular mechanisms. This review describes several molecular aspects of thyroid nodules oncogenesis, as well as its most promising diagnostic tumor markers. Following molecular pathways are described in particular: gene mutations, protein tumor markers, and epigenetic effects of micro-RNA, histones, as well as DNA methylation. The study of the pathogenesis of this disease has a prognostic value and contributes to the search for effective therapeutic and diagnostic methods and their improvement. That is why we also reviewed modern test panels aimed at preoperative differential diagnosis of thyroid nodules. Summarizing the results of world research on this topic allows us not only to expand the understanding of the fundamental processes of oncogenesis, but also to outline promising areas for future experimental research projects. All of that together will contribute to developing new prognostic, diagnostic and therapeutic technologies, and as a result, will improve the quality of medical care for patients with thyroid cancer.

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