Kanser Gelişimi ve Progresyonunda miRNA’LAR VE miRNA Gen Varyasyonları

2021 ◽  
Vol 6 (13) ◽  
pp. 38-45
Author(s):  
Nevra ALKANLI ◽  
Arzu AY
Keyword(s):  
Target Genes ◽  
Mirna Gene ◽  
Genetic Variations ◽  
Transcriptional Level ◽  
Mirna Genes ◽  
Non Coding Rna ◽  
Development Processes ◽  
New Treatment ◽  
Apoptosis Regulation ◽  
Regulatory Functions

MicroRNAs (miRNAs) are short non-coding RNA class and perform regulatory functions at the post transcriptional level as tumor suppressors or oncogenes. miRNAs are effective in cell differentiation, cell proliferation and apoptosis regulation in normal development processes. miRNA gene variations associated with gene silencing mechanisms, , pri-miRNA, pre-miRNA, mat-miRNA gene variations, genetic cariations in target sites of miRNAs have been identified. Significant changes may occur in miRNA expression levels as a result of genetic variations defined in miRNA genes. Therefore, it is thought that genetic variations in miRNA genes may be biomarkers that can play an important role in cancer formation, prognosis and progression. MiRNA function disorder due to miRNA-mediated dysregulation in target genes that may occur as a result of miRNA gene variations in the diagnosis and progression of various types of cancer should be evaluated. In addition, determining miRNAs and miRNA gene variations in target genes that affect drug behavior in increasing the effectiveness of drugs is very important in terms of developing new treatment methods and different therapeutic strategies for various cancer types. In this review, it is aimed to examine the potential roles of miRNAs and miRNA gene variations in cancer development, progression and treatment.

scholarly journals Bio Immune(G)ene Medicine and the Use of miRNAs to Regulate the Cell

2018 ◽  
Vol 1 (2) ◽  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Allergic Diseases ◽  
Degradation Process ◽  
Transcriptional Level ◽  
Collateral Damage ◽  
Rna Molecules ◽  
The Past ◽  
Needed Information ◽  
Non Coding Rna

MicroRNAs (miRNAs or miRs) are a type of non-coding RNA molecules that regulate the gene expression in a negative way, by downregulating the gene expression mainly at the post-transcriptional level, either by the mRNA degradation process or the inhibition of the translation. The role that many miRNAs play in the pathogenesis of several diseases is well known, such as in the inflammation process, in several steps of the oncogenesis or the metabolism of several virus and bacteria among many others. One of the main limitations in the therapeutic use of miRNAs is the ability to reach the target, as well as doing so without causing any collateral damage. One microRNA can indeed regulate up to 200 target-genes, and one gene can be influenced by a lot of different microRNAs. This is the purpose of the Bio Immune(G)ene Medicine: to achieve the cell without harm, use all the molecular resources available, especially epigenetic with the microRNAs, and to restore the cell homeostasis. The Bio Immune(G)ene Medicine only seeks to play a regulatory biomimetic role, to give the cell the needed information for its own right regulation. Our experience in cell regulation for the past few years has shown the way to fight, for instance, against the deleterious effects of viruses or bacteria in the lymphocytes, also at the background of many autoimmune or allergic diseases, as well as to regulate many other pathological processes. To fulfil this purpose, nanobiotechnology is used to reach the targets; we thus introduce very low doses of miRNAs in nano compounds with the aim to promote the regulation of the main signalling pathways disturbed in a given pathology.

scholarly journals Aberrant DNA methylation of miRNAs in Fuchs endothelial corneal dystrophy

2019 ◽  
Author(s):  
Peipei Pan ◽  
Daniel J. Weisenberger ◽  
Siyu Zheng ◽  
Marie Wolf ◽  
David G. Hwang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Target Genes ◽  
Mirna Gene ◽  
Corneal Dystrophy ◽  
Matrix Proteins ◽  
Corneal Endothelial Cells ◽  
Mirna Genes ◽  
Aberrant Dna Methylation

AbstractHomeostatic maintenance of corneal endothelial cells is essential for maintenance of corneal deturgescence and corneal transparency. In Fuchs endothelial corneal dystrophy (FECD), an accelerated loss and dysfunction of endothelial cells leads to progressively severe visual impairment. An abnormal accumulation of extracellular matrix is a distinctive hallmark of the disease, however the molecular pathogenic mechanisms underlying this phenomenon are not fully understood. We recently reported characteristic patterns of DNA methylation changes in the corneal endothelial cells of patients with FECD. Here, we investigate genome-wide and sequence-specific DNA methylation changes of miRNA genes in corneal endothelial samples derived from patients with FECD. We show that the majority of miRNA genes are hypermethylated at their promoter regions in FECD. More specifically, miR-199B is an extensively hypermethylated miRNA gene at its promoter region and its mature transcript miR-199b-5p was previously found to be almost completely silenced in FECD. Using a cell-based assay, we find that miR-199b-5p directly inhibits the expression of two epithelial mesenchymal transition (EMT)-inducing genes, Snai1 and ZEB1. Taken together, these findings suggest a novel regulatory mechanism of matrix protein production by corneal endothelial cells in which miR-199b-5p hypermethylation leads to its down-regulated expression and thereby the decreased expression of miR-199b-5p target genes, including Snai1 and ZEB1. Our results support miR-199b-5p as a potential therapeutic target to prevent or slow down the progression of FECD disease.Author summaryFuchs endothelial corneal dystrophy (FECD) due to corneal endothelial cell degeneration is one of the most common heritable causes of corneal visual loss and a leading indication for corneal transplantation. The progressive loss of corneal endothelial cells is accompanied by an abnormal deposition of extracellular matrix in the form of guttae. Here we discover that miRNA gene promoters are frequent targets of aberrant DNA methylation in FECD. In particular, we describe a novel epigenetic mechanism used by corneal endothelial cells to regulate extracellular matrix production. We find that miRNA-199b-5p functions as a negative regulator of Snai1 and ZEB1, two zinc finger transcription factors that have been shown to lead to increased production of extracellular matrix proteins. Furthermore, miR-199B was extensively hypermethylated in FECD and its mature transcript miR-199b-5p directly binds to the 3′-UTRs of Snai1 and ZEB1 genes. Ultimately, this may negatively modulate Snai1- and ZEB1-mediated production of extracellular matrix proteins. This work is the first to identify an important role of DNA methylation in the epigenetic regulation of miRNA-target genes in FECD and to describe a potential epigenetic biomarker for the treatment of FECD patients.

scholarly journals tRNA-Derived Small Non-Coding RNAs as Novel Epigenetic Molecules Regulating Adipogenesis

Biomolecules ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 274 ◽  
Author(s):  
Linyuan Shen ◽  
Zhendong Tan ◽  
Mailin Gan ◽  
Qiang Li ◽  
Lei Chen ◽  
...  
Keyword(s):  
Target Genes ◽  
Acid Synthesis ◽  
Differentially Expressed ◽  
Transcriptional Level ◽  
Gene Expressions ◽  
Intervention Treatment ◽  
Non Coding Rna ◽  
New Strategy ◽  
Triglyceride Content ◽  
Treatment Of Obesity

tRNA-derived fragments (tRFs), a novel type of non-coding RNA derived from tRNAs, play an important part in governing gene expressions at a post-transcriptional level. To date, the regulatory mechanism of tRFs governing fat deposition and adipogenesis is completely unknown. In this study, high fat diet was employed to induce an obese rat model, and tRFs transcriptome sequencing was conducted to identify differentially expressed tRFs that response to obesity. We found out that tRFGluTTC, which promoted preadipocyte proliferation by increasing expressions of cell cycle regulatory factors, had the highest fold change in the 296 differentially expressed tRFs. Moreover, tRFGluTTC also suppressed preadipocyte differentiation by reducing triglyceride content and lipid accumulation, and by decreasing expressions of genes that related to fatty acid synthesis. According to results of luciferase activity analysis, tRFGluTTC directly targeted Kruppel-like factor (KLF) 9, KLF11, and KLF12, thus significantly suppressing mRNA expressions of these target genes. Moreover, tRFGluTTC suppressed adipogenesis, accompanying by suppressing expressions of adipogenic transcription factors (aP2, PPARγ, and C/EBPα). In conclusion, these results imply that tRFGluTTC may act as a novel epigenetic molecule regulating adipogenesis and could provide a new strategy for the intervention treatment of obesity.

scholarly journals Overexpression of miR-1306-5p, miR-3195, and miR-3914 Inhibits Ameloblast Differentiation through Suppression of Genes Associated with Human Amelogenesis Imperfecta

2021 ◽  
Vol 22 (4) ◽  
pp. 2202
Author(s):  
Hiroki Yoshioka ◽  
Yin-Ying Wang ◽  
Akiko Suzuki ◽  
Meysam Shayegh ◽  
Mona V. Gajera ◽  
...  
Keyword(s):  
Potential Role ◽  
Target Genes ◽  
Expression Patterns ◽  
Mirna Gene ◽  
Amelogenesis Imperfecta ◽  
Transcriptional Level ◽  
Specific Expression ◽  
Protein Protein Interaction ◽  
Bioinformatic Tools ◽  
Non Coding Rnas

Amelogenesis imperfecta is a congenital form of enamel hypoplasia. Although a number of genetic mutations have been reported in humans, the regulatory network of these genes remains mostly unclear. To identify signatures of biological pathways in amelogenesis imperfecta, we conducted bioinformatic analyses on genes associated with the condition in humans. Through an extensive search of the main biomedical databases, we found 56 genes in which mutations and/or association/linkage were reported in individuals with amelogenesis imperfecta. These candidate genes were further grouped by function, pathway, protein–protein interaction, and tissue-specific expression patterns using various bioinformatic tools. The bioinformatic analyses highlighted a group of genes essential for extracellular matrix formation. Furthermore, advanced bioinformatic analyses for microRNAs (miRNAs), which are short non-coding RNAs that suppress target genes at the post-transcriptional level, predicted 37 candidates that may be involved in amelogenesis imperfecta. To validate the miRNA–gene regulation association, we analyzed the target gene expression of the top seven candidate miRNAs: miR-3195, miR-382-5p, miR-1306-5p, miR-4683, miR-6716-3p, miR-3914, and miR-3935. Among them, miR-1306-5p, miR-3195, and miR-3914 were confirmed to regulate ameloblast differentiation through the regulation of genes associated with amelogenesis imperfecta in AM-1 cells, a human ameloblastoma cell line. Taken together, our study suggests a potential role for miRNAs in amelogenesis imperfecta.

scholarly journals Aberrant DNA methylation of miRNAs in Fuchs endothelial corneal dystrophy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Peipei Pan ◽  
Daniel J. Weisenberger ◽  
Siyu Zheng ◽  
Marie Wolf ◽  
David G. Hwang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Endothelial Cells ◽  
Matrix Protein ◽  
Target Genes ◽  
Mirna Gene ◽  
Corneal Dystrophy ◽  
Gene Promoters ◽  
Corneal Endothelial Cells ◽  
Mirna Genes ◽  
Aberrant Dna Methylation

Abstract Homeostatic maintenance of corneal endothelial cells is essential for maintenance of corneal deturgescence and transparency. In Fuchs endothelial corneal dystrophy (FECD), an accelerated loss and dysfunction of endothelial cells leads to progressively severe visual impairment. An abnormal accumulation of extracellular matrix (ECM) is a distinctive hallmark of the disease, however the molecular pathogenic mechanisms underlying this phenomenon are not fully understood. Here, we investigate genome-wide and sequence-specific DNA methylation changes of miRNA genes in corneal endothelial samples from FECD patients. We discover that miRNA gene promoters are frequent targets of aberrant DNA methylation in FECD. More specifically, miR-199B is extensively hypermethylated and its mature transcript miR-199b-5p was previously found to be almost completely silenced in FECD. Furthermore, we find that miR-199b-5p directly and negatively regulates Snai1 and ZEB1, two zinc finger transcription factors that lead to increased ECM deposition in FECD. Taken together, these findings suggest a novel epigenetic regulatory mechanism of matrix protein production by corneal endothelial cells in which miR-199B hypermethylation leads to miR-199b-5p downregulation and thereby the increased expression of its target genes, including Snai1 and ZEB1. Our results support miR-199b-5p as a potential therapeutic target to prevent or slow down the progression of FECD disease.

In silico analysis of Single Nucleotide Polymorphisms Associated with MicroRNA Regulating 5-fluorouracil resistance in colorectal cancer

2021 ◽  
Vol 18 ◽  
Author(s):  
Seyed Hamid Moosavy ◽  
Shabnaz Koochakkhani ◽  
Mahdi Barazesh ◽  
Shiva Mohammadi ◽  
Khadijeh Ahmadi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Target Genes ◽  
Mirna Gene ◽  
Receptor Interaction ◽  
Seed Region ◽  
Inadequate Response ◽  
Hippo Signaling ◽  
Single Nucleotide ◽  
Mirna Genes

Background: The broad influence and reversible nature of microRNA (miRNA) on the expression and regulation of target genes lead to research suggest that miRNAs and Single nucleotide (SNPs) in miRNA genes interfere with 5-fluorouracil (5-FU) drug resistance in colorectal cancer chemotherapy. Methods: Computational assessment and cataloging of miRNA gene polymorphisms that target mRNA transcripts straightly or indirectly through regulation of 5-FU chemoresistance in CRC were screened out applying various universally accessible datasets such as miRNA SNP3.0 software. Results: 1255 SNPs in 85 miRNAs affecting 5-FU resistance (retrieved from literature) were detected. Computational analysis showed that 167 from 1255 SNP alter microRNA expression levels leading to inadequate response to 5-FU resistance in CRC. Among these 167 SNPs, 39 were located in the seed region of 25/85 miRNA and are more critical than other SNPs. Has-miR-320a-5p with 4 SNP in seed region was miRNA with the most number of SNP. On the other hand, it has been identified that proteoglycan in cancer, adherents junction, ECM-receptor interaction, Hippo signaling pathway, TGF-beta signaling cascade, biosynthesis of fatty acid, and fatty acid metabolism were the most important pathways targeted by these 85 predicted miRNAs. Conclusion: Our data suggest 39 SNPs in seed region of 25 miRNAs as catalog in miRNA genes that control the 5-FU resistance in CRC. These data also identify the most important pathways regulated by miRNA.

scholarly journals Regulatory Functions of MicroRNAs in Cancer Pathogenesis

2021 ◽  
Author(s):  
Mahafarin Maralani ◽  
Behzad Baradaran ◽  
Khalil Hajiasgharzadeh ◽  
Marc Peeters
Keyword(s):  
Large Family ◽  
Transcriptional Level ◽  
Messenger Rnas ◽  
Protein Coding ◽  
Rna Molecules ◽  
Cancer Pathways ◽  
Cancer Pathogenesis ◽  
Non Coding Rna ◽  
Genes Expression ◽  
Regulatory Functions

MicroRNAs (miRNAs) are a large family of evolutionary conserved small non-coding RNA molecules that firstly discovered in 1993. They regulate gene expression of about 50% of protein-coding genes at the post-transcriptional level. MiRNAs can target numerous messenger RNAs and subsequent misexpression of them can affect many different signaling pathways. They are playing a pivotal role in cancer development by regulation of the genes expression which involved in the proliferation, survival, differentiation, apoptosis or metastasis of the cancer cells. Several treatment approaches such as inhibition of oncomiRs and restoration of tumor suppressor miRNAs have been established in certain types of cancers and some other miRNA-based strategies are in development for cancer prevention and treatment. Nowadays, cancer is the most important target of miRNA therapeutics and the specific mechanisms by which miRNA mediates cancer pathways needs more research and study

scholarly journals Small Non-Coding-RNA in Gynecological Malignancies

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1085
Author(s):  
Shailendra Kumar Dhar Dwivedi ◽  
Geeta Rao ◽  
Anindya Dey ◽  
Priyabrata Mukherjee ◽  
Jonathan D. Wren ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
P Element ◽  
Gynecologic Malignancies ◽  
Diagnosis And Prognosis ◽  
Gynecological Malignancies ◽  
Non Coding Rna ◽  
Therapeutic Research ◽  
Regulatory Functions

Gynecologic malignancies, which include cancers of the cervix, ovary, uterus, vulva, vagina, and fallopian tube, are among the leading causes of female mortality worldwide, with the most prevalent being endometrial, ovarian, and cervical cancer. Gynecologic malignancies are complex, heterogeneous diseases, and despite extensive research efforts, the molecular mechanisms underlying their development and pathology remain largely unclear. Currently, mechanistic and therapeutic research in cancer is largely focused on protein targets that are encoded by about 1% of the human genome. Our current understanding of 99% of the genome, which includes noncoding RNA, is limited. The discovery of tens of thousands of noncoding RNAs (ncRNAs), possessing either structural or regulatory functions, has fundamentally altered our understanding of genetics, physiology, pathophysiology, and disease treatment as they relate to gynecologic malignancies. In recent years, it has become clear that ncRNAs are relatively stable, and can serve as biomarkers for cancer diagnosis and prognosis, as well as guide therapy choices. Here we discuss the role of small non-coding RNAs, i.e., microRNAs (miRs), P-Element induced wimpy testis interacting (PIWI) RNAs (piRNAs), and tRNA-derived small RNAs in gynecological malignancies, specifically focusing on ovarian, endometrial, and cervical cancer.

scholarly journals Dynamic characteristics and functional analysis provide new insights into long non-coding RNA responsive to Verticillium dahliae infection in Gossypium hirsutum

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guoning Wang ◽  
Xingfen Wang ◽  
Yan Zhang ◽  
Jun Yang ◽  
Zhikun Li ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Verticillium Wilt ◽  
Dynamic Characteristics ◽  
Target Genes ◽  
Acid Metabolism ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Alpha Linolenic Acid ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Background Verticillium wilt is a widespread and destructive disease, which causes serious loss of cotton yield and quality. Long non-coding RNA (lncRNA) is involved in many biological processes, such as plant disease resistance response, through a variety of regulatory mechanisms, but their possible roles in cotton against Verticillium dahliae infection remain largely unclear. Results Here, we measured the transcriptome of resistant G. hirsutum following infection by V. dahliae and 4277 differentially expressed lncRNAs (delncRNAs) were identified. Localization and abundance analysis revealed that delncRNAs were biased distribution on chromosomes. We explored the dynamic characteristics of disease resistance related lncRNAs in chromosome distribution, induced expression profiles, biological function, and these lncRNAs were divided into three categories according to their induced expression profiles. For the delncRNAs, 687 cis-acting pairs and 14,600 trans-acting pairs of lncRNA-mRNA were identified, which indicated that trans-acting was the main way of Verticillium wilt resistance-associated lncRNAs regulating target mRNAs in cotton. Analyzing the regulation pattern of delncRNAs revealed that cis-acting and trans-acting lncRNAs had different ways to influence target genes. Gene Ontology (GO) enrichment analysis revealed that the regulatory function of delncRNAs participated significantly in stimulus response process, kinase activity and plasma membrane components. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that delncRNAs participated in some important disease resistance pathways, such as plant-pathogen interaction, alpha-linolenic acid metabolism and plant hormone signal transduction. Additionally, 21 delncRNAs and 10 target genes were identified as being involved in alpha-linolenic acid metabolism associated with the biosynthesis of jasmonic acid (JA). Subsequently, we found that GhlncLOX3 might regulate resistance to V. dahliae through modulating the expression of GhLOX3 implicated in JA biosynthesis. Further functional analysis showed that GhlncLOX3-silenced seedlings displayed a reduced resistance to V. dahliae, with down-regulated expression of GhLOX3 and decreased content of JA. Conclusion This study shows the dynamic characteristics of delncRNAs in multiaspect, and suggests that GhlncLOX3-GhLOX3-JA network participates in response to V. dahliae invasion. Our results provide novel insights for genetic improvement of Verticillium wilt resistance in cotton using lncRNAs.

scholarly journals Waterlogging-Stress-Responsive LncRNAs, Their Regulatory Relationships with MiRNAs and Target Genes in Cucumber (Cucumis sativus L.)

2021 ◽  
Vol 22 (15) ◽  
pp. 8197
Author(s):  
Kinga Kęska ◽  
Michał Wojciech Szcześniak ◽  
Adela Adamus ◽  
Małgorzata Czernicka
Keyword(s):  
Target Genes ◽  
Recovery Period ◽  
Sufficient Information ◽  
Low Oxygen ◽  
Waterlogging Tolerance ◽  
Cucumis Sativus L ◽  
Waterlogging Stress ◽  
Non Coding Rna

Low oxygen level is a phenomenon often occurring during the cucumber cultivation period. Genes involved in adaptations to stress can be regulated by non-coding RNA. The aim was the identification of long non-coding RNAs (lncRNAs) involved in the response to long-term waterlogging stress in two cucumber haploid lines, i.e., DH2 (waterlogging tolerant—WL-T) and DH4 (waterlogging sensitive—WL-S). Plants, at the juvenile stage, were waterlogged for 7 days (non-primed, 1xH), and after a 14-day recovery period, plants were stressed again for another 7 days (primed, 2xH). Roots were collected for high-throughput RNA sequencing. Implementation of the bioinformatic pipeline made it possible to determine specific lncRNAs for non-primed and primed plants of both accessions, highlighting differential responses to hypoxia stress. In total, 3738 lncRNA molecules were identified. The highest number (1476) of unique lncRNAs was determined for non-primed WL-S plants. Seventy-one lncRNAs were depicted as potentially being involved in acquiring tolerance to hypoxia in cucumber. Understanding the mechanism of gene regulation under long-term waterlogging by lncRNAs and their interactions with miRNAs provides sufficient information in terms of adaptation to the oxygen deprivation in cucumber. To the best of our knowledge, this is the first report concerning the role of lncRNAs in the regulation of long-term waterlogging tolerance by priming application in cucumber.

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