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Molecular Oncology > Day 3: Notch, Beyond coding genes > Flashcards

Day 3: Notch, Beyond coding genes Flashcards

HC 08, 09, 10

1
Q

Discovery Notch

A

Drosophila wing variations in shape: smooth wing or notches in wig
> Crossing experiments to find spot in genome
> Notch gene
> Notch gene important in development

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2
Q

Loss Notch

A

Important role embryo development
> patterning nervous system lost in embryo

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3
Q

Protein Notch

A

-Transmembrane protein
-In plasma membrane, partly intracellular and extracellular
- EGF like modules: repeats

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4
Q

Humand have .. Notch genes

A

4

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5
Q

Conservation Notch gene

A

highly conserved

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6
Q

Developmental roles Notch

A
  • Differentiation
  • Proliferation
  • Cell death
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7
Q

Cell fate is controlled by …

A

Long range and local signalling

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8
Q

How does Notch act?

A

Local interactions
> contact-dependent signalling

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9
Q

How many human Notch receptors and ligands

A

4 receptors and 5 ligands
> all transmembrane
> extracellular domains can interact

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10
Q

Ligands Notch

A

Delta
> Dll1 & Dll4
> Jagged1 & Jagged2
> Dll3: decoy (inhibitory for signalling, binds but no signal transduction)

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11
Q

Activation Notch pathway

A

1 - Ligand binds to Notch receptor (bind)
2 - The NRR (negative regulatory region) domain becomes accessible (pull, ligand pulls receptor a bit out so that NRR is exposed)
3 - The ADAM protease cuts the extracellular part (cut)
4 - Gamma secretase cuts the intracellular part (cut)
5 - The NICD (Notch Intra-Cellular Domain) travels to nucleus and activates transcription

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12
Q

Where is the ADAM protease located

A

Transmembrane protein on cell with Notch receptor and cleaves NRR with extracellular protease domain

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13
Q

Cis inhibition (Notch)

A

Notch receiver cell or sending cell determined by ratio receptor and ligand
- Notch > ligand: receiver
- Notch < ligand: sender
> No activation sending cell when binding ligand to receptor: the pulling part is missing, ligand cannot pull for ADAM to cut, not the right conformation (own delta coupled to all notch, cannot pull)

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14
Q

Lateral inhibition

A
  • Notch activation inhibits ligand expression through pathway
  • Driven down by reception of signal > to receiving state
  • Locks cells into fate into Notch context
  • Through filopodia, sending cells can inhibit cells further than the neighbouring cells
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15
Q

Lateral inhibition: are the cells only on or off for Notch?

A
  • A lot of context surfaces possible: not on or off, but stronger and weaker senders and receivers based on spatial conformation
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16
Q

Organs where Notch is important for development

A

Heart, skeletal muscle, blood vessels, inner ear, nervous system

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17
Q

Role Notch signalling in gut

A
  • Stem cell maintenance in crypts
  • Cell fates
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18
Q

Organisation stem cells in intestinal crypt and notch

A

Stem cells and Paneth cells in alternative organisation
> stem cell is receiver
> Paneth cell is sender
> cells in locked states because lateral inhibition

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19
Q

Notch lateral inhibition in differentiation

A

-Secretory cells: receivers
-Absorptive cells: senders
> few receiving cells surrounded by all senders

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20
Q

Role Notch in cancer

A

Mostly oncogene
> in rare cancers: tumor suppressor

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21
Q

Role Notch in hallmarks cancer

A

> Metastatic behaviour: in EMT (oncogenic)
Notch is P53 suppressor (oncogenic)
Tumor suppressor role: Notch needed for macrophage polarization, immune system is changed when loss Notch

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22
Q

Change of Notch in cancer

A

Putative driver mutations in Notch1 > hotspot near C-terminus (possible gain of function): small domain/region
> many tumors have this same oncogenic mutation
(> tumor suppressor mutations more spread and not concentrated on one spot)

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23
Q

Where in Notch gene loss-of-function mutations

A

Middle and N-terminal region (spread, not concentrated same spot)

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24
Q

Other activation method of Notch except gain-of-function mutation

A

Notch copy number
> more copies: worse prognosis in metastatic CRC numbers
> drive Notch activation

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25
Q

Is Notch mutation solely enough to cause cancer?

A

No, it is part of driving tumorigenesis, is dangerous in combination with APC loss

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26
Q

Notch and implantation of cancers (xenograft)

A

Notch positive cells have much better ability to establish tumor after implantation

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27
Q

Notch and stemness of cell

A

Induced by Notch (also in normal cells)

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28
Q

KPN mice model

A

KRAS, p53 and Notch mutations > increased metastatic behaviour
> more EMT
> more mesenchymal gene expression profiles

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29
Q

Notch and immune system

A

Notch activation: make and secrete cytokines
> recruit neutrophils
> downregulate immune cells in tumor (T-cells)
> T-cells do not attack cancer, better survival of cancer
> more neutrophil infiltration

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30
Q

Blocking Notch leads to less neutrophil recruitment, why still useful for cancer

A

More T-cells infiltrate tumor > the CTLs are the ones that attack the tumor

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31
Q

Crosstalk Notch with other morphogen pathway

A

Wnt

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32
Q

Notch as target in cancer: which targets

A
  • Ligands > mAbs
  • Receptors > mAbs
  • Cleavage > Gamma secretase inhibitors
  • Transcriptional activation by NICD
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33
Q

Gamma secretase as target

A

Inhibit second cleavage to release NICD
> not a lot of success achieved: still progressive tumors
> increased dose shows increased Notch inhibition
> still not effective
> result in very few patients

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34
Q

Combinational therapy crenigacestat (gamma secretase inhibitor) with other drugs

A

Works better

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35
Q

Side effects Notch inhibition: where first problems?

A

GI tract first affected
> early effect because rapid dividing
> role Notch in stem cell environment and differentiation (gut morphology and homeostasis)

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36
Q

Which part of Notch is directly involved in transcriptional response upon Notch activation

A

NICD

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37
Q

How does a cell become a Notch sending cell (disregarding outside influence: lateral inhibition)

A

Cis-inhibition

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38
Q

Given that Notch has a role in maintaining stem cell state, do you expect it to be a oncogene or tumor suppressor gene?

A

Oncogene

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39
Q

HC09: Evolution and noncoding part DNA

A

This part increases with the complexity of organisms

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40
Q

Noncoding part human genome is 98%, how large part can be transcribed though?

A

over 70%

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41
Q

Discovery nuclein

A

Isolated nuclein > presence uracil > discovery DNA and RNA

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42
Q

Most abundant produced RNA

A

rRNA

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43
Q

rRNA function

A

> Form ribosomes with ribosomal proteins

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44
Q

Where production rRNA and systhesis ribosomes with proteins?

A

In the nucleolus
> organelle in nucleus by phase to phase separation

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45
Q

Formation nucleolus

A

By five acrocentric choromosomes
> short p-arm of chr. 13, 14, 15, 21, 22

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46
Q

How is the short p-arm from the acrocentric chromosomes which contribute to nucleolus called?

A

NOR: nucleolus organizing region

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47
Q

NOR consists of

A

Telomere, rDNA, centromere
> rDNA genes located at NOR (tandem repeats)
> trancription of the coding region only

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48
Q

Intergenic sites of rDNA is … transcribed

A

Not, only coding parts

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49
Q

Transcription rDNA genes

A

Transcription by RNA polymerase 1
> 18S rRNA
> 5.8S rRNA
> 28S rRNA
Transcription by RNA polymerase 3
> 5S rRNA (chromosome 1, not in nucleolus)

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50
Q

Assembly ribosomes

A

Transcription rRNA genes into large 45S pre-rRNA and 5S rRNA separately
Processing/modifications of pre-rRNA
Assembly to ribosomal subunits: 18S to 40S subunit with proteins and 5.8S, 28S and 5S with proteins to 60S ribosomal subunit
Export

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51
Q

mt-rRNAs

A

2 mt-rRNAs
> 16S mt-rRNA and 12S mt-rRNA
> encoded by mitochondrial DNA (mtDNA)
> Transcription by POLRMT
> (for mitochondrial translation)

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52
Q

Deregulation of rDNA in CRC

A

Intracellular increase Ca2+ in CRC cell from ER (together with Wnt pathway): emptied storages
> upregulation p-CaMKII (CaMK pathway) and p-UBF (via CaMK pathway)
> UBF involved in transcription of rDNA (part transcription complex to make 45S pre rRNA) > more rRNA made

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53
Q

Block upregulation rRNA transcription by:

A

Producing BAPTA-AM: chelator of Ca2+ (binder)

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54
Q

KO pre-45S rRNA

A

Induce cell cycle rest

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55
Q

Upregulation 45S pre-rRNA in cancer

A

Via pUBF
> for transcription of it in cancer cells

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56
Q

Cancer cells inhibit cell cycle arrest through

A

Inhibiting p53 through a pathway:
> APC inactivation
> Increased Ca2+
> Activation UBF
> Increasing rRNA levels
> maintain high level translation and prevent p53 dependent cell arrest

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57
Q

tRNA function

A

Coupling with amino acid and recognize mRNA codons
> close interaction tRNA with ribosome
> to assist elongation of polypeptide chain by supplying amino acids and recognizing genetic code

58
Q

Ribosome EPA

A

Exit site, peptidyl site, aminoacyl site

59
Q

tRNA has … codons

A

64 codons
> 61 AA codons
> 3 stop codons

60
Q

tRNA is transcribed by

A

RNA polymerase 3
> will stop after a stretch of 5 As (adenosines), forms U tail at 3 prime of tRNA

61
Q

Modifications of pre-tRNA

A
  • Cleavage 5’ leader (RNase P)
  • Cleavage 3’ poly U (RNase Z)
  • Splicing (TSEN/HSPC117)
  • Addition CCA triplet at 3’ prime
  • Aminoacylation at 3’ prime
62
Q

tRNA-derived small RNAs: tsRNA fates

A

tRNA halves (tiRNAs)
Small tRNA fragments (tRF)

63
Q

Formation tsRNAs is mediated by ….

A

Endoribonucleases
> DICER
> ANG (angiogenin)
> Rny1p

64
Q

tsRNA-dependent regulation of gene expression

A
  • Post-transcriptional silencing
  • Nascent RNA silencing
  • Transcriptional gene silencing
65
Q

tsRNA functions

A
  • Regulate stability of transcription
  • Histone tail modification
  • Translation regulation: prevent ribosome from translating, get RNA trapped in stress granules (YBX1 dependent), stall translation (decoy for elongation factors)
  • Cell cycle and proliferation regulation: decoy for cytochrome c
66
Q

5’tiRNA-His-GTG promotes CRC tumor growth, how?

A
  • Upregulated when hypoxia
  • Increase vasculature
  • Regulate LATS2 expression
    > Hypoxia: HIF-1a activates ANG transcription, ANG processes tRNA to form tiRNA
    > LATS2 is known player in hypoxia pathway and phosphorlates YAP for degradation or inactivation: the tiRNA inactivates transcription LATS: YAP actively to nucleus for target genes
    > anti-apoptosis: tumor survival and pro-proliferation
67
Q

How does 5’tiRNA-His-GTG interfere with LATS2

A

Interfere with endogenous DNA fragment for transcription block

68
Q

Tumor grows faster than vasculature can handle leads to …

A

hypoxia
> pathway initiated for 5’tiRNA-His-GTG via HIF-1a and ANG

69
Q

Which RNA type is part of the central dogma

A

mRNA

70
Q

RNAs are the …. of DNA

A

final effectors
> because also role noncoding RNAs

71
Q

snRNA (small nuclear RNA) function

A

Involvement in splicing

72
Q

RNA splicing by the spliceosome, name the route

A

5’ exon-intron junction: U1 binds
3’ exon-intron junction: U2 binds
Formation spliceosome: U4, 5, 6 recruited (snRNPs, small nuclear ribonucleoproteins, with protein)
Excised intron in lariat shape

73
Q

Name the snRNAs from the major spliceosome, minor spliceosome and histone splicing

A

Major spliceosome
> U1
> U2
> U4
> U5
> U6
Minor spliceosome
> U11
> U12
> U5
> U4atac
> U6atac
Histone splicing
> U7

74
Q

Difference major and minor spliceosome in humans

A

Recognize different introns

75
Q

Transcription snRNAs by…

A

RNA polymerase 2
only U6 by RNA polymerase 3 (stops after 5 T segment)

76
Q

What happens with snRNA after transcription

A

Quickly exported to cytoplasm: interaction with different proteins
> 3 prime trimming, maturation
> nuclear import snRNA: accumulate in splicing speckles

77
Q

Deregulation U2 snRNPs in CRC

A

SF3B3 upregulated in cancer (part of U2, splicing factor)
> mTOR splicing: from exon skipping to inclusion new exon (that is the mutant, no alternative splicing of mTOR pre-mRNA)
> mTOR no longer promoting apoptosis but mitigating it because exon 8 inclusion
> induce EMT features because inclusion mTOR exon 8 by high SF3B3
> aggressive cancer

78
Q

snoRNA discovery (small nucleolar RNA)

A

Released from 28S rRNA by heat
> rRNA interacts with snoRNA in nucleolus

79
Q

Transcription snoRNA by …

A

RNA polymerase 2

80
Q

snoRNAs DNA are often located in …

A

introns

81
Q

Types of snoRNAs

A

C/D (SNORDs) and H/ACA

82
Q

Difference C/D and H/ACA snoRNAs in maturation process

A

Associate with different proteins
> different snoRNPs (ribonucleoproteins)

83
Q

Production process snoRNPs

A

Transcription > splicing > debranching > exonucleolytic processing

84
Q

Different complementariy C/D box and H/ACA box for snoRNA

A

C/D box is triggered to methylation after complementary annealing rRNA (2’O-methylation)
H/ACA box: triggered by target rRNA binding > uridine to pseudouridine (pseudouridinylation)

85
Q

Functions snoRNA for rRNA

A

Catalyze modifications of rRNAs (2’O-methylation and pseudouridylation)
> rRNA modifications impact RNA stability and translation efficiency of ribosomes

86
Q

snoRNAs and cleavage

A

Some snoRNAs (both C/D and H/ACA box) required for cleavage pre-rRNAs
> interactions at cleavage sites

87
Q

snoRNAs have diverse roles. What is the primary function

A

Modification of rRNAs and snRNAs (including cleavage of rRNAs)
> Targeting is guided by complementarity

88
Q

Silencing and KO of snoRNAs

A

Silencing: cell proliferation goes up
KO: regulate oncogenes

89
Q

Upregulated snoRNA in CRC

A

SNORD11B
(> present: more methylation, more repression MeUA in primer before RT in experiment when low dNTP: RT more efficient)
> SNORD11B dependent (2’-O) methylation of miRNA let-7 promotes its degradation, prevents downregulation of key oncogenic proteins in CRC (RAS, MYC, YAP)
» C/D box

90
Q

H19 is first discovered ncRNA in human. Only expressed in … allele and IGF2 only in … allele

A

Maternal, paternal
> noncoding RNAs
> different enhancers

91
Q

Xist only expressed when

A

XX > for X chromosome inactivation
> shield the X chromosome
> an RNA, no open reading frame

92
Q

HC10: Discovery of the first miRNA: Lin-14 and Lin-4

A

Expression during C. elegans larval stages
> LacZ gene fused with 3’UTR of interest: blue staining
> Lin-14 only expressed in early larval stages
> Lin-4 (miRNA) mutant, also in later stages, no degradation RNA of Lin-14 via miRNA Lin-4

93
Q

Regulation of miRNA

A

By transcription of miRNAs

94
Q

Expression Lin-4 on western blot

A

> 61 and 22 nts fragments on western blot
Hairpin pre-miRNA (66 nts) and muture active miRNA (22 nts)

95
Q

Large gap between identification first and second miRNA (lin4 and let-7), why?

A

Technical limitations and lack of awareness of miRNAs, more focus protein coding

96
Q

Let-7 expression in larval stages C elegans

A

Similar role as Lin4
> Let-7 expression goes up from L4>adult stages of C. elegans
> Lin4 from L1>L2

97
Q

The let-7 sequence is very … in many species

A

conserved

98
Q

Length miRNAs

A

21-24 nts
> 2600 encoded in human genome

99
Q

miRNAs are relatively … ncRNAs

A

small

100
Q

Biogenesis miRNAs and function

A

-RNA polymerase 2: transcription
-Highly structured hairpins in pri-miRNA (primary) are recognized by proteins which remove separate hairpins (pre-miRNA)
-Export to cytosol
-Cytosolic proteins: cleavage to mature miRNA and strand selection (one strand selected) > (RNA Induced Silencing Complex (RISC) formed with proteins)
-Translation inhibition or mRNA degradation by binding target mRNA (complementary) (removal cap)
> degradation preferred

101
Q

miRNA target sites

A

What is the most important feature to predict miRNA target sites?&raquo_space;
-5 prime
-Seed sequence nt-2-8 is conserved: 5’
-3’ prime supplementary pairing lacks predictive values
-miRNA and mRNA are partially complementary

102
Q

miRNA in cancer

A

Downregulated
> miRNA promotes differentiation
> miRNA inhibited, no differentiation, stemness kept

103
Q

Repression of miRNA expression levels in cancer

A

-Mutations (biogenesis route)
- DNA methylation (CpG island on gene promotor/enhancer)
- Uridylation (TUT4/TUT7) > target miRNA for degradation (add stretch of urindine U on miRNA)
- Upregulation snRNA (SNORD11B)

104
Q

miRNA as tumor suppressors: let-7

A

Reduction of let-7 levels prevents negative regulation of RAS
> promotes cell proliferation and tumor growth (MAPK activation, Mek Erk route)

105
Q

Oncogenic miRNAs

A

Upregulated in cancer (this is the minority, majority is tumor suppressor)
> miR17-92 cluster in lymphoma
> similar seed sequence in cluster (same transcripts targeted?)
> Overexpressing Myc: get lymphoma in mice model: more severe and faster tumor growth and transformation of cells when lacking let7

106
Q

Tsix

A

ncRNA
> important for regulation Xist transcription
> Reverse transcription on Xist site (transcriptional interference): inhibit expression Xist > Tsix masks Xist RNA domain
> Tsix enhances Xist RNA degradation

107
Q

Air ncRNA

A

Together with Igf2r receptor expressed (maternal allele)
> Air only on paternal allele
> Forces Igf2r receptor to be expressed on maternal allele
> forcing paternal and maternal alleles to interact with each other

108
Q

Big boom miRNA discovery around 2000s, why?

A

NGS available

109
Q

HOTAIR

A

Interacts with chromatin modifiers: modulate histone tails and condensation of DNA
> lncRNA

110
Q

PCGEM1

A

Interacts with TFs which interacts with enhancers and promotors
> help with transcription endogenously
> linker between enhacer and promotor via TFs
> lncRNA

111
Q

MALAT1

A

lncRNA
> interaction with miRNAs and splicing factors (snRNA)

112
Q

Mechanisms of lncRNA actions

A

-Guide: for chromatin modifying enzyme
-Scaffold: for transcriptional proteins
-Decoy: bind trancriptional protein so that it does not bind DNA
-lncRNA sponging miRNA: bind and occupy it (clean it)
-lncRNA as miRNA precursor
-Chromatin looping (like PCGEM1)

113
Q

lncRNA biogenesis

A

-Transcription by RNAP II
-Capped and polyadenylated
-Little ORF (open reading frame)
-Some ORFs are a bit translated to little peptides
> Not entirely noncoding always
-RNase P cleaves 3’ prime UTR to get tRNA-like structure and release it
-Or release miRNA like structures (stem loop/hairpin)

114
Q

lncRNA CRNDE function in CRC

A

Epigenetically repress cdk1a (cell cycle inhibitor is repressed for G1 progression)
> associate with negative transcription proteins (PRC2 complex) to epigenetically repress cdk1a gene
> lncRNA

115
Q

KO CRNDE

A

The complex (PRC2 complex) which can bind p21 is less present
> reduction repressive mark
> switch off transcription cdk1a is stopped: increase cdk1a > inhibit cell proliferation

116
Q

CCAT2 in CRC

A

CCAT2 activates Myc expression (upregulated in CRC)
> lncRNA
> CCAT2 interacts with TCF7L2 > for Wnt target gene transcription, needed for full expression of Myc
> other factors are attracted which support CCAT2

117
Q

Enhancers are much bound by factors like CBP (Creb binding protein, cofactor for RNA pol 2) and POL2, which kind of RNAs support these

A

eRNA: enhancer RNA

118
Q

Enhancer RNA biogenesis and types

A

Short-bidirectional eRNAs (more rare)
> short half life
> Bidirectional transcription
> unspliced
> nonpolyadenylated
Long-unidirectional eRNAs (more widespread, capped)
> Long half life
> Unidirectional transcription
> spliced
> polyadenylated

119
Q

Where production eRNAs?

A

Enhancer regions bound by RNA polymerase 2

120
Q

eRNA biogenesis

A
  • Enhancer domain active (eg H3K27ac)
  • Enhancer bound by TFs/GTFs/Pol2
  • Transcription initiation leading to RNA capping by CBC (cap binding complex)
  • Elongation is regulated by p-TEFb
  • Termination is mediated by Integrator (endonuclease) and WDR82/PP1 (pol2 dephosphorylation)
  • RNA exosomes degrade eRNAs from 3’ to 5’
121
Q

Mechanisms of eRNAs o influence transcription

A
  • establishment and/or stabilization of enhancer-promotor looping
  • intervening with trancription machinery
  • trapping transcription factor and co-activator
  • regulation of histone modifications (eg recruit CBP (acetylation) or PRC2 (me3) to promote or inhibit modifications)
122
Q

ETS2 eRNA (ETS2e) in CRC

A

Upregulated in CRC
> super-enhancers activated (many enhancers close to each other)
> DNA gets opened up (eRNAs produced)
> in graph, much H3K27ac upstream (or downstream) promotor

123
Q

SNP involved in Crohns disease> increased risk CRC > why?

A

T-variation ETS2e (ETS2 eRNA): more ETS2 produced
> eRNA in super-enhancers upregulated
> more ETS2 transcription because high ETS2e
> > ETS2 is oncogene

124
Q

ETS2e variation C/T SNP

A

SNP (C/T) in ETS2e creates binding motif for MECOM which drives the expression of eRNAs and higher expression of ETS2
> more ETS2 > IBD, CRC

125
Q

circRNA function

A

circular RNA
> can sponge (clean, get rid of) miRNA (loss of function)

126
Q

Biogenesis circRNA

A
  • During transcription ncRNA or mRNA
  • During splicing
  • Embedded elements interact > close together to transcript
  • back splicing favoured (instead of linear splicing in mRNA): circle formed
  • Only with exons, can be one exon, can include introns
127
Q

Mechanisms of action circRNAs

A
  • miRNA sponges or decoys
  • protein sponges or decoys
  • enhancer of protein function
  • protein scaffolding
  • protein recruitment (for example TF to loci or to subcellular component)
  • templates for translation (production unique circRNA peptides)
128
Q

circRNA and CRC

A

Can increase cell proliferation
> circRNA from SKA3 mRNA (back-splicing of one of the exons) > has-circ-0000467
» overexpression: Myc goes up (proliferation)
» E-cadherin goes down (EMT induced)
» cdkn down (less cell cycle control, proliferation)

129
Q

How does circRNA help with translation of Myc

A
  • Interact with 3’UTR of Myc
  • Bind elongation factor
  • Interact with translation initiation factor for Myc
  • More Myc > more metastasis, proliferation and migration
130
Q

Relative RNA expression circ467 and SKA3 when RNase R+ or RNase R- (RNase R treatment)
(skip this maybe)

A

RNA expression circ467 for both present
RNA expression SKA3 absent for RNase R+

131
Q

C/D box snRNAs main function

A

methylation rRNA

132
Q

Which nucleotides is for binding of miRNA

A

Seed sequence: nt2-8, (first ten)

133
Q

lncRNA can interact with?

A

-Protein
-mRNA
-miRNA

134
Q

eRNAs mainly function … (cis/trans)

A

in cis

135
Q

Name functions rRNA, tRNA, snRNA and snoRNA in cancer

A
  • rRNA: transcription increases (Ca2+ dependent) to support proliferation and prevent p53 stress response
  • tRNA: fragments with different functions (eg miRNA like) can be generated by endonucleases (eg Dicer and Ang)
  • snRNA: splicing can be influenced (inclusion vs skipping) by deregulation of splicing factors
  • snoRNA: influence stability of other RNA (eg let-7a miRNA)
136
Q

miRNA function name (RNA?)

A

Post-transcriptional regulation: RNAi

137
Q

lncRNAs are gene expression regulators: how

A
  • Bind chromatin modifiers (eg PRC2)
  • Interact with TFs (eg AR)
  • Sponge/decoy miRNAs or proteins (eg malat1)
138
Q

eRNAs (1D, 2D (directional, unidirectional long living or bidirectional short living) functions as transcription regulators

A
  • Bind chromatin modifiers (eg PRC2, CBP/p300)
  • Stabilize chromatin structure (eg cohesin, mediator)
  • interact with TFs (eg YY1)
  • interact with transcription cofactors (eg BRD4)
139
Q

circRNA as gene expression regulators

A
  • bind chromatin modifiers (eg TET1)
  • sponge/ decoy miRNAs or proteins
  • serve as scaffold
  • can be translated to produce peptides
140
Q

miRNAs, lncRNAs, eRNAs and circRNAs in CRC

A
  • miRNAs: mostly downregulated in CRC (mutations/biogenesis), can also exert oncogenic functions: miR17-92
  • lncRNAs: often deregulated in cancer (eg CRNDE/PRC2 and CCAT2/TCF7L2)
  • eRNAs: often epigenetically deregulated in cancer (activated or repressed), occasionally, genetic changes or predispositions (SNPs) can modulate eRNA expression (eg ETS2e)
  • circRNA: back-splicing as well as function of circRNAs can be deregulated in cancer (eg has-circ-0000467/MYC)
141
Q

insert kahoot questions

A

Molecular Oncology (7 decks)

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