Figure 4: Pan-cancer oncomiRs are grouped into a coregulated superfamily of pan-oncomiRs.
From: Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif
(a) Broadly conserved pan-cancer oncomiRs (45.4%) share a central GUGC seed sequence homology, grouping them into a larger oncomiR ‘superfamily’ consisting of miR-17, -19, -130, -210, -18 and -455 seeds. (b) MicroRNA superfamilies often target complementary ‘super seeds’. (c) Overview of target predictions for the top 3,000 highest-ranked TS for miR-17, -19, -130, -210 -18 and -455 families demonstrates TS cotargeting relationships with 39.2% of miR-17/106a/93 targets, 70.2% of miR-19 targets, 79.3% of miR-130/301ab targets, 42.3.0% of miR-18a targets, 75.7% miR-455 targets and 62.5% of miR-210 targets having predicted cotargeting with at least one other superfamily member. The miR-93 family has largely the same predicted target spectrum as that of the miR-17 family. miR-210 has few AGO-CLIP-defined targets and was thus not included in the Venn. miR-93 is grouped with the miR-17 family in this analysis, because their target spectrums almost completely overlap. The microRNA-17, -19 and -130 families most heavily mediate pan-cancer cotargeting. (d) miR-17-19-130 superfamily members are strongly correlated across pan-cancer tumours, demonstrating potent coregulation of these microRNAs (P<1E-200, Student’s t-test). MicroRNAs are colour-coded based on co-localization to the same genomic cluster. microRNA–microRNA correlate n-values are as follows: BLCA=95, BRCA=794, COAD=177, HNSC=301, KIRC=466, LAML=173, LUAD=313, LUSC=193, ovarian carcinoma (OV)=225, READ=65 and uterine corpus endometrioid carcinoma (UCEC)=320.
