Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif.
MicroRNAs modulate tumorigenesis through suppression of specific genes. As many tumour types rely on overlapping oncogenic pathways, a core set of microRNAs may exist, which consistently drives or suppresses tumorigenesis in many cancer types. Here we integrate The Cancer Genome Atlas (TCGA) pan-cancer data set with a microRNA target atlas composed of publicly available Argonaute Crosslinking Immunoprecipitation (AGO-CLIP) data to identify pan-tumour microRNA drivers of cancer. Through this analysis, we show a pan-cancer, coregulated oncogenic microRNA 'superfamily' consisting of the miR-17, miR-19, miR-130, miR-93, miR-18, miR-455 and miR-210 seed families, which cotargets critical tumour suppressors via a central GUGC core motif. We subsequently define mutations in microRNA target sites using the AGO-CLIP microRNA target atlas and TCGA exome-sequencing data. These combined analyses identify pan-cancer oncogenic cotargeting of the phosphoinositide 3-kinase, TGFβ and p53 pathways by the miR-17-19-130 superfamily members.
Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza Houston M822, Houston, Texas 77030, USA.
Mark P
MP
Hamilton
Kimal
K
Rajapakshe
Sean M
SM
Hartig
Boris
B
Reva
Michael D
MD
McLellan
Cyriac
C
Kandoth
Li
L
Ding
Travis I
TI
Zack
Preethi H
PH
Gunaratne
David A
DA
Wheeler
Cristian
C
Coarfa
Sean E
SE
McGuire
D020413:3' Untranslated Regions; D000465:Algorithms; D020816:Amino Acid Motifs; D063646:Carcinogenesis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D005810:Multigene Family; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger; C495901:TP53 protein, human; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases