Jul 14, 2014 - Genes Transcription Factor of DNA Binding Sites & Gene Regulation - BIOBASE Biological ... Find an example via RPPA or mutations. 45 ...
Beyond Argonaute: understanding microRNA dysregulation in cancer and its effects on protein interaction and transcriptional regulatory networks Sara JC Gosline, PhD ISMB – Late Breaking Research July 14, 2014
microRNAs (miRNAs) • Transcribed in nucleus • Processed by Dicer • Forms silencing complex with argonaute (Ago2) and GW182 • Binds 3’ untranslated region (UTR) of mRNA
Drosha Nucleus Cytoplasm Dicer
• Causes premature degradation of mRNA
AAAA
GW182
Ago2 1
Seed region sequence complementarity enables computational prediction of targets
AAAA
GAUGGAG CUACCUCA
AAAA
2
-2
-1 0 1 mRNA expression change 12h after miR-7 over-expression
2
miR-7 Targets Other mRNA
0
0.0
miR-7 Targets Other mRNA
Number of mRNA 1000 2000 3000 4000 5000 6000
Fraction less than value 0.8 0.6 0.2 0.4
1.0
miRNAs impose modest fold change
-2
-1 1 0 mRNA expression change 12h after miR-7 over-expression
Grimson et al., Mol. Cell 2007
3
2
1.0
Yet miRNAs are implicated in many biological processes
0.0
Let-7 Targets Other mRNA
-2
-1 0 1 mRNA expression change 32h after let-7 over-expression
2
0
Fraction less than value 0.8 0.6 0.2 0.4
Number of mRNA 2000 4000 6000
Let-7 Targets Other mRNA
-2
-1 1 0 mRNA expression change 32h after let-7 over-expression
Selbach et al., Nature 2008
2
4
Available Cancer Types
# Cases Shipped by BCR
# Cases with Data*
Date Last Updated (mm/dd/yy)
200
200
02/04/14
The Cancer Genome Atlas (TCGA) Acute Myeloid Leukemia [LAML]
6/26/2014
Cancer Details - Breast invasive carcinoma: Case Counts - Data Portal
Adrenocortical carcinoma [ACC]
80
80
06/13/14
Bladder Urothelial Carcinoma [BLCA]
412
366
06/25/14
Brain Lower Grade Glioma [LGG]
516
516
06/25/14
1064
06/24/14
257
06/25/14
Breast invasive carcinoma [BRCA] Home
Download Data
Tools
About the Data
1101
Publication Guidelines
Cervical squamous cell carcinoma and endocervical Home > Cancer Details adenocarcinoma [CESC]
308
Cholangiocarcinoma [CHOL]
36
0
Colon [COAD] carcinoma samples: Target adenocarcinoma number of Breast invasive
462
450
06/23/14
185
176
06/15/14
Anno
Breast invasive carcinoma: Case Counts 500 (number subject to change)
Head and Neck squamous cell carcinoma [HNSC] 528 528 1 Raw exome data are available at CGHub. Variant calling data are available via the links under Exome above.
Clinical 1001 06/23/14 N/A
06/25/14
We focus on six cancers with >50 mRNA and miRNA levels
2 Organ-Specific Controls are derived from donor material taken from individuals not matched to the tumors in this study. Specifically,
these tissues would be from [KICH] individuals that did not have cancer but were able66 to donate tissue for other autopsy Kidney Chromophobe 66 reasons (e.g. rapid 06/25/14
5
We can search for miRNAs with expression correlated with survival
High miRNA levels correlate with better outcome Low miRNA levels correlate with better outcome
