Fig. 1: Genome-wide binding of MSI2 to different regions of its target genes. | Cell Death Discovery

Fig. 1: Genome-wide binding of MSI2 to different regions of its target genes.

From: MSI2 promotes translation of multiple IRES-containing oncogenes and virus to induce self-renewal of tumor initiating stem-like cells

Fig. 1

A MSI2 is upregulated in HCC patients’ tumors vs. normal samples listed in TCGA datasets. Representative box-whisker plots showing MSI2 expression across 374 tumors and 50 normal samples. Nonoverlapping confidence intervals at 95% indicate that expression levels between two groups differ in the population means (*). Numbers in parentheses represent patients in the corresponding group. B MSI2 overexpression is correlated with poor survival of HCC patients in TCGA data analysis. C The diagram shows the step-by-step workflow for RNA-Immuno-Precipitation sequencing. Immunoblot uncropped file was included in Supplementary Information. D The pie charts show the genome-wide binding pattern of MSI2. Significant binding was observed within introns, coding regions as well as 3′UTRs and 5′UTRs. E Pathway enrichment analysis in 177 identified MSI2 binding partners as detected by MSI2-RIP-seq (FDR p < 0.05, log2 ratio of enrichment ≥ ±1). A ranked p-value was computed for each pathway based on hypergeometric distribution along with Benjamin–Hochberg correction (p < 0.05). F A Venn diagram shows the identification of a set of 11 significant MSI2 binding targets from genome-wide RIP-seq and RNA-seq approaches; of these 11 genes MYC and miR-22 are reported to be associated in various cancers. G MSI2 binds to MYC mRNA and miR22hg. Enrichment analysis using Burrows-Wheeler Aligner (BWA) from data for MSI2 shows enriched binding in the exonic regions of MYC and miR22hg. Representative genomic snap shots of enriched binding within the MYC (coding region) and miR-22 (ncRNA). Vertical dashed lines in MYC snapshot indicate transcription start sites (TSS). H Venn diagram shows number of MSI2-interacting genes shared among present study and previously published MSI2 RIP-seq results. MSI2-interacting genes shared among the present study and previously published MSI1 or MSI2 iCLIP-seq results (10,394 – 221 = 10,173 genes: MSI1 CLIP-Seq data: GSE54598). MSI2 iCLIP-seq results (4162 – 403 = 3759 genes: MSI2 iCLIP-Seq data. I Gene set enrichment analysis (GSEA) shows enrichment for HCC oncogenesis, self-renewal, and stemness as well as RNA metabolism pathways in MSI2 RIP-seq analyses.

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