the role of miRNA in cancer

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

Contents:

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

Introduction

M.Koolivand MSc 4

Cancer definition

M.Koolivand MSc 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 6

EPIDEMOLOGY OF CANCER

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.

M.Koolivand MSc 8

M.Koolivand MSc 9

miRNA Role In Cell

Cell Cycle

Differentiation Apoptosis

Cell MetabolismDevelopment

M.Koolivand MSc 10

M.Koolivand MSc 11

M.Koolivand MSc 12

M.Koolivand MSc 13

M.Koolivand MSc 14

Development & Differentiation

M.Koolivand MSc 15

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.

M.Koolivand MSc 17

M.Koolivand MSc 18

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

M.Koolivand MSc 20

M.Koolivand MSc 21

M.Koolivand MSc 22

M.Koolivand MSc 23

M.Koolivand MSc 24

M.Koolivand MSc 25

Examples

M.Koolivand MSc 26

M.Koolivand MSc 27

M.Koolivand MSc 28

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™

M.Koolivand MSc 30

Example

Metastatic breast cancer lung cancer

Pancreatic CancerHepatocellular Carcinoma

M.Koolivand MSc 31

M.Koolivand MSc 32

Conclusion

Progresses on the biology of miRNAs greatlyenhance 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 miRNAsis in its infancy.

M.Koolivand MSc 33

1.http://www.biooncology.com/molecular-causes-of-cancer 2. https://www.qiagen.com3. http://www.nature.com/4. http://www.ncbi.nlm.nih.gov/pubmed 5. http://www.sciencedirect.com6. https://scholar.google.com 7. http://www.slideshare.net/ 8. https://www.linkedin.com/ 9.http://wikipedia.org

مهدوی. 10 مجید مولکولی و سلولی شناسی زیست11. María José Bueno, Marcos Malumbres, Cell Division and Cancer Group, Spanish National Cancer

Research Center (CNIO), Madrid, Spain, MicroRNAs and the cell cycle

Resources:

M.Koolivand MSc 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 cancer13. 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 cancer16. 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 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 36

26. MicroRNAs in Cervical Cancer: Evidences for a miRNA ProfileDeregulated by HPV and Its Impact on Radio-ResistanceAbraham 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.

M.Koolivand MSc 37

Thanks For Your Attention