the role of miRNA in cancer
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1) The document discusses microRNAs (miRNAs) and their role in cancer, including how they regulate key cellular processes and pathways involved in cancer development. 2) miRNAs are generally downregulated in cancer and can be deregulated through various mechanisms that allow cancer cells to escape miRNA-mediated repression. 3) The document explores using circulating miRNAs as biomarkers for cancer diagnosis and monitoring treatment response, though more research is still needed to understand their biological functions outside of cells.
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the role of miRNA in cancer
- 1. Follow up miRNA In Cancer Supervised by : Dr.Moein Presented by : Mohsen Koolivand MSc student of Clinical Biochemistry September 2015 Hormozgan University of Medical Sciences Faculty of Medicine Bandar Abbas, Iran
- 2. Contents: M.Koolivand MSc 2 Introduction Of Cancer Investigate The Molecular Mechanisms Of Cancer Introduction of miRNA miRNA Role In Cell The Use Of miRNA For Diagnosis and Treatment Of Cancer Conclusion Resources
- 5. The Molecular Mechanisms Of Cancer • Genomic instability and mutations • Evading growth suppressors • enabling replicative immortality • Activating invasion and metastasis • tumor promote inflammatory • Angiogenesis • evading immune destruction • sustaining proliferative signaling • Reprogramming energy metabolism M.Koolivand MSc 5
- 6. M.Koolivand MSc 6 EPIDEMOLOGY OF CANCER
- 7. M.Koolivand MSc 7 Introduction of miRNA MicroRNAs (miRNAs) are endogenous small noncoding RNAs (20 – 23 nucleotides) that negatively regulate the gene expressions at the posttranscriptional level by base pairing to the 3' untranslated region of target messenger RNAs. Hundreds of miRNAs have been identified in humans and evolutionarily conserved from plants to animals. It is revealed that miRNAs regulate various physiological and pathological pathways such as cell differentiation, cell proliferation, and tumoriogenesis.
- 9. M.Koolivand MSc 9 miRNA Role In Cell Cell Cycle Differentiation Apoptosis Cell Metabolism Development
- 14. M.Koolivand MSc 14 Development & Differentiation
- 16. M.Koolivand MSc 16 Apoptosis Apoptosis describes the orchestrated collapse of a cell characterised by membrane blebbing, cell shrinkage, condensation of chromatin, and fragmentation of DNA followed by rapid engulfment of the corpse by neighbouring cells. It is distinguished from death by necrosis by the absence of an associated inflammatory response.
- 19. M.Koolivand MSc 19 miRNA Role In Cancer 1- miRNAs are generally downregulated in cancer 2- Mechanisms for miRNA deregulation and escape from miRNA- mediated repression 3- miRNA regulation of key cancer-related pathways
- 29. M.Koolivand MSc 29 The Use Of miRNA For Diagnosis and Treatment Of Cancer Circulating miRNAs in cancer: from detection to Therapy Detection methods to quantify serum miRNAs in cancerpatients Methods qRT-PCR TaqMan miRNA array Microarray TaqMan low density array NanoString-nCounter microRNA assays LNA™
- 30. M.Koolivand MSc 30 Example Metastatic breast cancer lung cancer Pancreatic CancerHepatocellular Carcinoma
- 32. M.Koolivand MSc 32 Conclusion Progresses on the biology of miRNAs greatly enhance our understanding of their functions with respect to basic mechanisms of oncogenesis and diagnostics and prognostics. cell-free miRNAs might play an increasing role as non-invasive tools for the detection of cancer in early stages and as biomarker to monitor prognosis and response to therapy. However, knowledge on the biological functions of extracellular miRNAs is in its infancy.
- 33. 1.http://www.biooncology.com/molecular-causes-of-cancer 2. https://www.qiagen.com 3. http://www.nature.com/ 4. http://www.ncbi.nlm.nih.gov/pubmed 5. http://www.sciencedirect.com 6. https://scholar.google.com 7. http://www.slideshare.net/ 8. https://www.linkedin.com/ 9.http://wikipedia.org 10.مهدوی مجید مولکولی و سلولی شناسی زیست 11. María José Bueno, Marcos Malumbres, Cell Division and Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain, MicroRNAs and the cell cycle M.Koolivand MSc 33 Resources:
- 34. 12. Martin D. Jansson, Anders H. Lund, Biotech Research and Innovation Centre and Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark, MicroRNA and cancer 13. Shan Deng,1 George Adrian Calin,4 Carlo M. Croce,5 George Coukos1-3 and Lin Zhang1,2, 1Center for Research on Early Detection and Cure of Ovarian Cancer; 2Department of Obstetrics and Gynecology; 3Abramson Family Cancer Research Institute; University of Pennsylvania; Philadelphia, Pennsylvania USA; 4Department of Experimental Therapeutics; Department of Cancer Genetics; University of Texas; MD Anderson Cancer Center; Houston, Texas USA; 5Departments of Molecular Virology; Immunology and Medical Genetics; Ohio State University; Columbus, Ohio USA, Mechanisms of microRNA deregulation in human cancer 14. Fazli Wahid a, Adeeb Shehzad a, Taous Khan b,⁎, You Young Kim a,⁎, a School of life Sciences and Biotechnology, College of Natural sciences, Kyungpook National University, 1370 Sangeok-dong, Buk-ku, Taegu 702-701, Korea b Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan, MicroRNAs: Synthesis, mechanism, function, and recent clinical trials 15. Minlee Kim1,2 and Frank J Slack2, MicroRNA-mediated regulation of KRAS in cancer 16. Jingcao Huang1,2, Hui Lyu1, Jianxiang Wang2, Bolin Liu1, 1Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 2State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China M.Koolivand MSc 34
- 35. 17. Benjamin L Jackson1*, Anna Grabowska1 and Hari L Ratan1,2, MicroRNA in prostate cancer: functional importance and potential as circulating biomarkers 18. Wen-Tao Wang and Yue-Qin Chen*, Circulating miRNAs in cancer: from detection to therapy 19. Srivatsava Naidu, Peter Magee and Michela Garofalo*, MiRNA-based therapeutic intervention of cancer 20. Veronica Balatti*, Yuri Pekarky and Carlo M Croce, Role of microRNA in chronic lymphocytic leukemia onset and progression 21. Ingrid Garajová,1,2 Tessa Y. Le Large,1 Adam E. Frampton,3 Christian Rolfo,4 Johannes Voortman,1 and Elisa Giovannetti1,5, Molecular Mechanisms Underlying the Role of MicroRNAs in the Chemoresistance of Pancreatic Cancer 22. M Jovanovic1,2 and MO Hengartner1,, 1Institute of Molecular Biology, University of Zurich and ETH Zurich, Zurich, Switzerland and 2PhD Program in Molecular Life Sciences, University of Zurich and ETH Zurich, Zurich, Switzerland, miRNAs and apoptosis: RNAs to die for 23. Dr. Manash K. Paul,Department of Biology,Indian Institute of Science Education and Research,Mohali; www.iisermohali.ac.in, Cancer and Therapeutics 24. Webinar, February 23rd , 2012, Adam Baker, PhD. adam@exiqon.com , microRNA discovery and biomarker development in clinical samples 25. Kaveri Sidhu†, Neetu Rohit Kapoor†,Vijaya Pandey† andVijay Kumar* Virology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India, The “macro” world of microRNAs in hepatocellular carcinoma M.Koolivand MSc 35
- 36. M.Koolivand MSc 36 26. MicroRNAs in Cervical Cancer: Evidences for a miRNA Profile Deregulated by HPV and Its Impact on Radio-Resistance Abraham Pedroza-Torres 1,7, Eduardo López-Urrutia 1,2, Verónica García-Castillo 2, Nadia Jacobo-Herrera 3, Luis A. Herrera 4, Oscar Peralta-Zaragoza 5, César López-Camarillo 6, David Cantú De Leon 4, Jorge Fernández-Retana 1,2, Jorge F. Cerna-Cortés 7 and Carlos Pérez-Plasencia 1,2,8,* 27. QIAGEN GeneGlobe Pathways Molecular Mechanisms of Cancer 28.
- 37. Thanks For Your Attention 37M.Koolivand MSc
Editor's Notes
- li
- کل MicroRNAs: Synthesis, mechanism, function, and recent clinical trials Defects in the miRNA Biogenesis Pathway IN Mechanisms of microRNA deregulation in human cancer
- In complex organisms, miRNAs regulate a wide range of biological processes, including development, differentiation, proliferation, cell metabolism and apoptosis (programmed cell death). Dysregulation of individual or subset of miRNAs is linked with the pathogenesis of human diseases, such as cancer, cardiovascular disorders, viral infections and metabolic diseases. The first insight into their function was a result of phenotypic studies of mutations that disrupt basic components of the miRNA pathway. As mentioned before, the primary role of miRNAs is gene regulation; today it is know that they regulate the expression of more than 10 000 genes in a single cell. Such cellular effects of miRNAs can be seen in a myriad of different cells – i.e. in cancer cells, cardiovascular cells or skin cells. MicroRNA Cellular Functions
- اخر Mechanisms of microRNA deregulation in human cancer
- نقش اپی ژنتیک و از دست نویس های ترجمه ای تو برگه اچاراااا Epigenetic control of cellular differentiation Since each cell, regardless of cell type, possesses the same genome, determination of cell type must occur at the level of gene expression. While the regulation of gene expression can occur through cisand transregulatory elements including a gene’s promoter and enhancers, the problem arises as to how this expression pattern is maintained over numerous generations of cell division. As it turns out, epigenetic processes play a crucial role in regulating the decision to adopt a stem, progenitor, or mature cell fate. This section will focus primarily on mammalian stem cells. In systems biology and mathematical modeling of gene regulatory networks, cellfate determination is predicted to exhibit certain dynamics, such as attractorconvergence (the attractor can be an equilibrium point, limit cycle or strange attractor) or oscillatory.[18] Importance of epigenetic control The first question that can be asked is the extent and complexity of the role of epigenetic processes in the determination of cell fate. A clear answer to this question can be seen in the 2011 paper by Lister R, et al. [19] on aberrant epigenomic programming in human induced pluripotent stem cells. As induced pluripotent stem cells (iPSCs) are thought to mimic embryonic stem cells in their pluripotent properties, few epigenetic differences should exist between them. To test this prediction, the authors conducted wholegenome profiling of DNA methylation patterns in several human embryonic stem cell (ESC), iPSC, and progenitor cell lines. Female adipose cells, lung fibroblasts, and foreskin fibroblasts were reprogrammed into induced pluripotent state with the OCT4, SOX2, KLF4, and MYC genes. Patterns of DNA methylation in ESCs, iPSCs, somatic cells were compared. Lister R, et al. observed significant resemblance in methylation levels between embryonic and induced pluripotent cells. Around 80% of CG dinucleotides in ESCs and iPSCs were methylated, the same was true of only 60% of CG dinucleotides in somatic cells. In addition, somatic cells possessed minimal levels of cytosine methylation in nonCG dinucleotides, while induced pluripotent cells possessed similar levels of methylation as embryonic stem cells, between 0.5 and 1.5%. Thus, consistent with their respective transcriptional activities,[19] DNA methylation patterns, at least on the genomic level, are similar between ESCs and iPSCs. However, upon examining methylation patterns more closely, the authors discovered 1175 regions of differential CG dinucleotide methylation between at least one ES or iPS cell line. By comparing these regions of differential methylation with regions of cytosine methylation in the original somatic cells, 4449% of differentially methylated regions reflected methylation patterns of the respective progenitor somatic cells, while 5156% of these regions were dissimilar to both the progenitor and embryonic cell lines. In vitroinduced differentiation of iPSC lines saw transmission of 88% and 46% of hyper and hypomethylated differentially methylated regions, respectively. Two conclusions are readily apparent from this study. First, epigenetic processes are heavily involved in cell fate determination, as seen from the similar levels of cytosine methylation between induced pluripotent and embryonic stem cells, consistent with their respective patterns of transcription. Second, the mechanisms of dedifferentiation (and by extension, differentiation) are very complex and cannot be easily duplicated, as seen by the significant number of differentially methylated regions between ES and iPS cell lines. Now that these two points have been established, we can examine some of the epigenetic mechanisms that are thought to regulate cellular differentiation. Mechanisms of epigenetic regulation Pioneering factors (Oct4, Sox2, Nanog) Three transcription factors, OCT4, SOX2, and NANOG – the first two of which are used in iPSC reprogramming – are highly expressed in undifferentiated embryonic stem cells and are necessary for the maintenance of their pluripotency.[20] It is thought that they achieve this through alterations in chromatin structure, such as histone modification and DNA methylation, to restrict or permit the transcription of target genes. Polycomb repressive complex (PRC2) In the realm of gene silencing, Polycomb repressive complex 2, one of two classes of the Polycomb group (PcG) family of proteins, catalyzes the diand trimethylation of histone H3 lysine 27 (H3K27me2/me3).[21][20][22] By binding to the H3K27me2/3tagged nucleosome, PRC1 (also a complex of PcG family proteins) catalyzes the monoubiquitinylation of histone H2A at lysine 119 (H2AK119Ub1), blocking RNA polymerase II activity and resulting in transcriptional suppression.[20] PcG knockout ES cells do not differentiate efficiently into the three germ layers, and deletion of the PRC1 and PRC2 genes leads to increased expression of lineageaffiliated genes and unscheduled differentiation.[20] Presumably, PcG complexes are responsible for transcriptionally repressing differentiation and developmentpromoting genes.
- Molecular Mechanisms Underlying the Role of MicroRNAs in the Chemoresistance of Pancreatic Cancer
- MicroRNAs in Cervical Cancer: Evidences for a miRNA Profile Deregulated by HPV and Its Impact on Radio-Resistance
- Role of microRNA in chronic lymphocytic leukemia onset and progression
- Circulating miRNAs in cancer: from detection to therapy
- Example A positive feedback between p53 and miR-34 miRNAs mediates tumor suppression Molecular Mechanisms Underlying the Role of MicroRNAs in the Chemoresistance of Pancreatic Cancer
- Circulating miRNAs in cancer: from detection to Therapy MicroRNA and their involvement in anticancer drug resistance. Drug resistance can occur at many levels, including drug efflux, alterations in drug target, DNA repair, cell cycle regulation, and evasion of apoptosis. Some selected miRNAs which have been demonstrated to alter these mechanisms are shown in this figure :Molecular Mechanisms Underlying the Role of MicroRNAs in the Chemoresistance of Pancreatic Cancer The “macro” world of microRNAs in hepatocellular Carcinoma Application of MicroRNA in Diagnosis and Treatment of Ovarian Cancer Mechanisms and role of microRNA deregulation in cancer onset and progression
- Finally, although there are large numbers of reports on the functions of miRNAs in the development of cancer, the complex gene networks affected by them remains a considerable problem. The complex relationships between miRNAs and their functional pathways must be demonstrated. With the understanding of the origin, stability, their role in cell-cell communication and advances in methods to detect circulating miRNAs, we believe that, in the future, they will become a cancer buster: From detection to therapy.