Paper Discussion Flashcards
(20 cards)
What are miRNAs?
A class of 17- to 27-nucleotide single-stranded RNA molecules that regulate gene expression post-transcriptionally
The focus of the paper is:
A) Review the involvement of lncRNA in cancer
B) Review the involvement of rRNA in cancer
C) Review the involvement of miRNA in cancer
C) review the involvement of miRNA in cancer
What are SNPs?
Single nucleotide polymorphisms are variations in a single DNA base pair within a genome
Where have miRNAs been found to be aberrantly expressed?
A) pancreas
B) colon
C) liver
D) all of the above
D) all of the above
True or false: miRNAs can be used as therapeutic tools
True
True or false: anti-miRNA bind directly to miRNA, blocking its activity.
True
True or false: miRNAs participate in keeping the balance of genes regulating networks that determine’s a cell’s fate.
True
True or false: miRNAs can contribute to tumorigenesis by modulating the expression of proteins that directly regulate circuitry controlling cellular life and death decisions
True
True or false: Drosha is a ribonuclease
True
True or false: the first evidence of aberrant miRNA expression in human cancers was described in B-cell chronic lymphocytic leukemia
True
Describe the mechanism of the biogenesis of miRNAs.
The miRNA gene is transcribed, which creates a pri-miRNA, which is cleaved by Drosha, then exported into the cytoplasm. It’s then cleaved into a ds-RNA by Dicer. One strand of it is then selected to function as mature miRNA, and the other strand is likely degraded.
Describe the miRNP complex
A mature miRNA strand is loaded into the miRNA ribonucleoprotein (miRNP) complex. Single or multiple miRNA copies bind to mRNA 3’ untranslated regions (UTR).
What are the two mechanisms of control of miRNA?
miRNAs that bind mRNA with perfect complementarity lead to mRNA degradation, and imperfect binding leads to inhibition of translation.
What can cause abnormal miRNA expression?
SNPs, epigenetic changes, chromosomal abnormalities, and defects in the biogenesis machinery (changes in something like Drosha or Dicer)
What are miRNA mimics?
Synthetic double-stranded RNA molecules designed to mimic the function of endogenous miRNAs.
Their presence increases mRNA silencing, which leads to decreased protein levels. (this is called gene silencing)
Discuss the limitations of using miRNA as a therapeutic tool.
miRNA stability (needs to be bound to a scaffold to be stable); miRNA is double stranded despite the fact that RNA does not form helices, so miRNA forms pseudohelices instead, which is a form of self-protection.
Method of delivery: could use viruses as delivery methods to solve the problem of ‘how are you going to get it to where it needs to be?’
Side effects: you’re bound to affect something else, so you gotta ask yourself the degree of impact
Discuss whether or not epigenetics has a role in the regulation of miRNA
Hypo- and hyper-methylation both have roles in the regulation of expression of miRNA genes
What’s the impact of mutations in mr-15 miR15A & miR-16-1?
Lymphocytic leukemia and familial breast cancer
miR-21 and miR-106 miRNAs have been established in the later steps of tumorigenesis progression and metastasis. Discuss the outcome of suppression of miR-21.
In metastatic breast cancer cells had reduced invasion and metastasis.
In malignant hepatocyte cells there was reduced invasion and metastasis.
How do target protectors regulate miRNA?
target protectors are a type of therapeutics that is specifically looking to target the seed regions of miRNA. They’re small oligonucleotides with perfect complementarity to the seed regions. The seed region is different for each of the miRNAs, so even though binding at the seed region is a common characteristic, that seed region is still going to be different, so that’s what you use target protectors for.
