miR-155 is a microRNA that plays an important role in regulating immune cell development and function. It is highly expressed in lymphocytes like B cells and T cells. miR-155 regulates lymphocyte immune responses by targeting various molecules and pathways. It controls B cell and T cell differentiation, antibody production, and cytokine secretion. Dysregulation of miR-155 has been implicated in several diseases like cancers and autoimmune disorders. Due to its role in diseases, miR-155 is a potential therapeutic target for developing new treatments.

1. “ROLE OF miR-155 IN THE
REGULATION OF LYMPHOCYTE
IMMUNE FUNCTION”
INDIAN VETERINARY RESEARCH INSTITUTE
IZATNAGAR-243122

2. MASTER
MAESTRO

3. Introduction
Biogenesis and mechanism of action
Evolutionary conservation
Targets and Tissue distribution
Regulation
Therapeutic aspects
Future prospects
Conclusion

4. NON-CODING RNA: FORMERLY
KNOWN AS “JUNK”
http://catalyst.harvard.edu
miRNA

5. CHARACTERISTICS OF miRNA
 Small non-coding double stranded RNA.
 Approximately 19-22 nucleotide long.
 Repress activity of complementary mRNAs.
 Regulate 30% of mammalian gene products.
 miRNAs show phenomena of multiplicity and
cooperativity.
 Have been described in invertebrates and vertebrates:
worms, fungi, plants, and mammals.
 Many are conserved between vertebrates and invertebrates.
Xiao and Rajewsky, 2009 and http://catalyst.harvard.edu

6. miRNA GENES
 ~60% of miRNAs are expressed independently.
 ~15% of miRNAs are expressed in clusters.
 ~25% of miRNAs are in introns.

7. WHAT IS miR-155 ?
 MiR-155 is a microRNA that in humans is encoded by the
MIR155 host gene or MIR155HG.
 Formerly called as BIC (B-cell Integration Cluster).
 It was later found that the MIR155HG was composed of
three exons within human chromosome 21 (Hsa21 band
q21.3).
 The MIR155HG RNA transcript does not contain a long
open reading frame (ORF).
Mol. Cell. Biol. 17 (3): 1490–502

8. BIOGENESIS
Advances.nutrition.org

10. Micro RNA silencing via many mechanism-
1)Inhibition of intiation
2)Post inhibiton initiation
3)m-RNA degradation- (a) Decapping
(b) Deadenylation
Mechanism of action of miRNA

11. Evolutionary Conservation
 Sequence of pre-mir-155 and miR-155-5p was conserved
between human, mouse, and chicken.
 miR-155-5p express more conserved sequences in 22
different organisms including mammals, amphibians, birds,
reptiles, sea squirts, and sea lampreys.
 Less sequence data is available regarding miR-155-3p.
Teng G, Papavasiliou Faraoni I, Antonetti FR, Cardone J, Bonmassar E (2009)

12. WHERE IS MY TARGET

13. HERE IS SOMETHING MORE
?

14. TARGAETS

15. CONTD....

16. PREDICTION OF COMMON
CONSERVED SEED REGION

17. SITES THAT ARE CONSERVED , MORE RESPOND
SITES FALLING IN ORFs FEW RESPOND
SITES IN FAVORABLE PREDICTED CONTEXT MORE
RESPOND (Grimson et al., 2007)
mRNAS WITH MORE SITES, MORE RESPONSE
(Grimson et al., 2007)
miRNAs WITH STRONGER SEED PAIRING ,MORE
EFFECTIVE (Garcia et al., 2011)
miRNAs WITH FEWER TARGET m-RNAs MORE
EFFECTIVE (Garcia et al., 2011)
CONTD....

18. TISSUE DISTRIBUTION
 miR-155 pri-miRNA was abundantly expressed in the spleen
and thymus.
 miR-155 detectable in the liver, lung, and kidney.
 miR-155 expression is specific for hematopoietic cells including
B-cells,T-cells, monocytes and granulocytes.
 Expression levels of miR-155-3p were 20-200 fold less when
compared to miR-155-5p levels.

19. REGULATION
Recent miRNA deletion studies have revealed a
central role in the regulation of the immune response.
The deletion of miRNA-155 impaired T and B cell
differentiation in germinal centers.
 Greatly decreased antibody and cytokine production.

20. REGULATION OF LYMPHOCYTE
An Overview of Regulation by miR-155

21. REGULATION OF T-LYMPHOCYTE

22. CONCEPT TO REGULATE IMMUNE
FUNCTIONS
UP
REGULATION
DOWN
REGULATION
POSITIVE NEGATIVE
Goal
HOMEOSTASIS
STABLIZATION

23. HOW miR-155 REGULATE T- LYMPHOCYTE
IMMUNE FUNCTION
 Regulation of differentiation into the memory or effector
phenotypes of T cells .
 Control of T-cell differentiation: to favour Th1 responses partially
by modulating cytokine production .
 Control of proliferation and homeostasis of Treg cells by stabilizing
the signal of FOXP3 through the targeting of SOCS1.

24. MOLECULAR BASIS REGULATION
PLoS ONE (2012) Yao R, Ma YL, Liang W, Li HH, Ma ZJ, Yu X, Liao YH

25. CONTD…
IL-2
FOXP3
miR-155
c-Maf
IL-4
production
Th2
Phenotype
IFN-Y and IL
—2 release

26. ROLE OF Mir-155 IN REGULATION OF B-
LYMPHOCYTE
miR-155
Molecules ISSN 1420-3049 www.mdpi.com/journal/molecules 2014

27. HOW miR-155 REGULATE B- LYMPHOCYTE
IMMUNE FUNCTION
 Control of B-cell differentiation and GC reaction: activation
and function of B cell in germinal centres and for T-cell
dependent antibody responses by negatively modulating
somatic hypermutation and class-switch recombination
through the targeting of AID and PU.1 .
 Required for normal production of isotype-switched, high
affinity IgG1 antibodies in B-cells
Molecules ISSN 1420-3049 www.mdpi.com/journal/molecules 2014

28. MOLECULAR BASIS REGULATION
Mark A. Lindsay, Trends in Immunology Vol.29 No.7347 cell

29. ROLE OF Mir-155 IN LYMPHOCYTE IMMUNE
FUNCTION
An overview

30. OVERVIEW OF REGULATION BY
DIFFERENT PATHWAY AND OUTCOME
Immunology Review: Nabila Seddiki,Vedran Brezar,Nicolas Ruffin,Yves Levy
and Sanjay Swaminathan

32. THERAPEUTIC ASPECTS

33. THERAPEUTIC APPROACH

34. CANCER
Lung cancer, Breast cancer, B-cell lymphomas

35. CONTD…

36. HYPERTENSION AND CARDIOVASCULAR
DISEASES
Mir-155
REGULATION OF
AGTR1 GENE
DOWNREGULATION
OF AGTR1 PROTEIN
HYPERTENSION
DOWN-MODULATES
INFLAMMATORY
CYTOKINE
PRODUCTION
DECREASES AS
PROGRESSION

37. FUTURE PROSPECTS
 MiR-155 serves as important targets in cancer therapy.
 Nanoparticle-based therapy in an in- vivo microRNA-155.
 Suggesting a promising therapeutic option for lymphoma/leukemia.
 We show that systemic delivery of antisense peptide nucleic acids
encapsulated in unique polymer nanoparticles inhibits miR-155 and
slows the growth of these “addicted” pre-B-cell tumors in vivo.
 miRNAs in disease diagnosis and therapy as biomarkers miR-155.

38. CONCLUSION
 miR-155 IS A HIGHLY EXPRESSED AND IMPORTANT miRNA WITH
FUNCTIONAL RELEVANCE IN THE BIOLOGY OF LYMPHOCYTES
 DYSREGULATION OF miR-155 HAS BEEN SHOWN TO HAVE RELEVANCE
IN A NUMBER OF HUMAN TUMOURS, AUTOIMMUNE DISEASES AND
RESPONSES TO VIRAL INFECTIONS BY T CELLS AND B CELLS
 miR-155 IN LYMPHOCYTES IN VARIOUS DISEASE STATES, MAY LEAD TO
THE IDENTIFICATION OF NEW PROTEIN TARGETS THAT LEAD TO
NOVEL THERAPIES FOR THESE CONDITIONS
 miR-155, IN CONCERT WITH OTHER MIRNAS, REGULATE GENE
FUNCTION IN LYMPHOCYTES AND ALSO THEIR PRECISE ROLE IN
DISEASE PATHOGENESIS

39. POINEER WORKER
Victor Ambros Gary Bruce Ruvkun
David Baulcombe
Craig C. MelloAndrew Z. Fire

40. REFERENCES
 Requirement of bic/microRNA-155 for normal immune function Rodriguez
A, Vigorito E, Clare S et al. Science 2007.
 New regulators of immune cell development and function- Nat Immunol
Baltimore D, Boldin MP, O’Connell RM, Rao DS, Taganov KD.
MicroRNAs: 2008.
 SOCS,inflammation,andautoimmunity -AkihikoYoshimura, MayuSuzuki ,
RyotaSakaguchi ,ToshikatsuHanada and HideoYasukawa.
 Challenges and Opportunities of MicroRNAs in Lymphomas -Giacoma De
Tullio , Vincenza De Fazio , Nicola Sgherza , Carla Minoia , Simona
Serratì ,Francesca Merchionne , Giacomo Loseto , Angela Iacobazzi ,
Antonello Rana ,Patrizia Petrillo , Nicola Silvestris , Pasquale Iacopino ,and
Attilio Guarini :MOLECULE 2014
 A role for miR-155 in enabling tumor-infiltrating innate immune cells to
mount effective antitumor responses in mice -Zonari E, Pucci F, Saini M,
Mazzieri R, Politi LS, Gentner B, Naldini L.. Blood 2013.
 Role of miR-155 in the regulation of lymphocyte immune function and
disease-Nabila Seddiki, Vedran Brezar,Nicolas Ruffin, Yves Levy, and
Sanjay Swaminathan