Figure 4.
Molecular perturbation induced by MIR17PTi in pMM cells. (A) Hierarchical clustering of pMM cells (n = 4; patients 5, 6, 7, and 9) exposed for 6 days to MIR17PTi (2.5 µM) or equimolar scr-NC. (B) Table of gene sets from the Hallmark collection enriched with genes upregulated by MIR17PTi (positive phenotype) in sensitive pMM cells (patients 5, 6, 7, and 9). Number of genes in each set (size), the normalized enrichment score (NES), and test of statistical significance (false discovery rate [FDR] q value) are highlighted. (C) Enrichment plots of 3 representative transcriptional signatures of MYC-upregulated target genes in the positive phenotype of sensitive pMM cells exposed to MIR17PTi (2.5 µM) for 6 days. (D) Venn diagram–intersecting genes upregulated by MIR17PTi with genes predicted to be miR-17-92 targets (by miRcode) and genes validated as miR-17-92 interactors in CLIP sequencing experiments (starBase v2.0). (E) Representation of MYC/miR-17-92 FFLs. In red are reported genes with a fold change (FC) increase >1.5. (F) qRT-PCR analysis of pri-mir-17-92 and BIM, BZW2, DUSP2, NAP1L1, or VDAC1 messenger RNAs (mRNAs) in pMM cells (n = 3) exposed to MIR17PTi (2.5 µM) for 6 days. The results shown are average pri-mir-17-92 or mRNA expression levels after normalization with glyceraldehyde-3-phosphate dehydrogenase and ΔΔCt calculations. *P < .05.

Molecular perturbation induced by MIR17PTi in pMM cells. (A) Hierarchical clustering of pMM cells (n = 4; patients 5, 6, 7, and 9) exposed for 6 days to MIR17PTi (2.5 µM) or equimolar scr-NC. (B) Table of gene sets from the Hallmark collection enriched with genes upregulated by MIR17PTi (positive phenotype) in sensitive pMM cells (patients 5, 6, 7, and 9). Number of genes in each set (size), the normalized enrichment score (NES), and test of statistical significance (false discovery rate [FDR] q value) are highlighted. (C) Enrichment plots of 3 representative transcriptional signatures of MYC-upregulated target genes in the positive phenotype of sensitive pMM cells exposed to MIR17PTi (2.5 µM) for 6 days. (D) Venn diagram–intersecting genes upregulated by MIR17PTi with genes predicted to be miR-17-92 targets (by miRcode) and genes validated as miR-17-92 interactors in CLIP sequencing experiments (starBase v2.0). (E) Representation of MYC/miR-17-92 FFLs. In red are reported genes with a fold change (FC) increase >1.5. (F) qRT-PCR analysis of pri-mir-17-92 and BIM, BZW2, DUSP2, NAP1L1, or VDAC1 messenger RNAs (mRNAs) in pMM cells (n = 3) exposed to MIR17PTi (2.5 µM) for 6 days. The results shown are average pri-mir-17-92 or mRNA expression levels after normalization with glyceraldehyde-3-phosphate dehydrogenase and ΔΔCt calculations. *P < .05.

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