Diseases 2 🙄 Flashcards
(22 cards)
Which pathway is mutated in ALL?
Fusion proteins act on DROSHA to increase oncogene miRNA 191
How can miRNA cause cancer?
Act like tumour suppressors to regulate pro-apoptosis proteins
Act like oncogenes to inhibit tumour suppressors
What can be a cause of CML?
Overexpression of miR-17-92 inhibits regulator of PI3K signalling
How can CLL be treated?
Synthetic analogues of miR-15a and miR-16
What can be a cause of CLL?
Deletion of miR-15a and 16 which regulate expression of anti-apoptosis BCL2 proteins
Results in overexpression of anti-apoptosis
How can miRNAs be treated?
Sponges
Supplement loss
S Mwt compounds
Antisense oligos
Give an example of supplementing loss of exons by aberrant splicing
SMaRT to deliver alternative tags contain pre-splicing mRNA in cystic fibrosis
How can antisense oligos be stabilised?
Locked ribose rings/ nucleic acids (2OMeth) improves affinity
Anti-miR-122 in HCV
How does HCV manipulate cellular miR-122?
Binds ahead of IRES to stabilise genome
Promotes replication
What is the molecule in trials to treat HCV miR-122?
Miravastin
How can loss of miRNA expression be corrected?
Supplementing gene using viral vectors or crispr-cas
How is melanoma treated?
Anti miR-182 sponge
BROADLY How can miRNA be treated?
Decrease/Increase cell mRNA
Decrease/increase miRNA
Give an example of a latency associated transcript?
SV40 miR-S1 decreases T Ag to evade immune response during latency
KSHV miR-K5 for Bcl-2 pro-apoptosis proteins
Herpes miR-H2-3p for ICPO
How do viruses affect miRNA?
Encode viral miRNA
Alter production / activity of cellular miRNA
An example of a viral miRNA?
Adenovirus VA1 decreases DROSHA activity
How does herpes use viral miRNA?
LAT (ncRNA) is pri-miRNA for 4 miRNA to suppress lytic lifecycle
MiRNA overlap lytic genes such as ICPO
Which viruses encodes most miRNA?
EBV :23
How can plants and bacteria use viRNA?
Incorporated into genome to create miRNA through crispr-cas
Give examples of pathways controlled by miRNA?
30-75% all mRNA
Cell cycle
Metabolism
Immune differentiation
Apoptosis
Why is miRNA targeting risky?
Multiple miRNAs per pathway AND multiple pathways per miRNA
How does KSHV use miRNA?
Evades apoptosis during latency using 12 pre-miRNAs but 17 miRNAs from a single locus