Figure 4
Figure 4. Targeting of STAT6 and GATA3 by miR-135b in ALCL. (A) Up-regulation of miR-135b target genes was evaluated on NPM-ALK knockdown using GSEA (dataset GSE6184). (B) Heat map showing the expression of Th17-related molecules, GATA3, FOXO1, and other ALCL-related genes (GZMB, PRF1, and TCR-related genes) in PTCL. Gene expression data are derived from GSE19069. In addition to GATA3, FOXO1 expression in ALCL was also lower than those in other PTCLs. ATLL indicates adult T-cell leukemia/lymphoma; AITL, angioimmunoblastic T-cell lymphoma; and PTCLu, PTCL-unclassifiable. (C) Sequence alignment between miR-135b and its putative binding sites in the STAT6 and GATA3 3′UTRs. (D) miR-135b targets STAT6 and GATA3. Luciferase activity of the STAT6 and GATA3 3′UTR reporter constructs with wild-type or mutated target site (shown in panel C) in HEK293T cells cotransfected with empty vector, miRNA-lacZ expression control vector (miRNA for lacZ), or pri-miR-135b expression vector [miR-135b (+)]; ***P < .001). (E) Up-regulation of STAT6 and GATA3 by TuD-RNA–mediated miR-135b inhibition in Karpas 299 cells. The quantification results were shown in the right panel.

Targeting of STAT6 and GATA3 by miR-135b in ALCL. (A) Up-regulation of miR-135b target genes was evaluated on NPM-ALK knockdown using GSEA (dataset GSE6184). (B) Heat map showing the expression of Th17-related molecules, GATA3, FOXO1, and other ALCL-related genes (GZMB, PRF1, and TCR-related genes) in PTCL. Gene expression data are derived from GSE19069. In addition to GATA3, FOXO1 expression in ALCL was also lower than those in other PTCLs. ATLL indicates adult T-cell leukemia/lymphoma; AITL, angioimmunoblastic T-cell lymphoma; and PTCLu, PTCL-unclassifiable. (C) Sequence alignment between miR-135b and its putative binding sites in the STAT6 and GATA3 3′UTRs. (D) miR-135b targets STAT6 and GATA3. Luciferase activity of the STAT6 and GATA3 3′UTR reporter constructs with wild-type or mutated target site (shown in panel C) in HEK293T cells cotransfected with empty vector, miRNA-lacZ expression control vector (miRNA for lacZ), or pri-miR-135b expression vector [miR-135b (+)]; ***P < .001). (E) Up-regulation of STAT6 and GATA3 by TuD-RNA–mediated miR-135b inhibition in Karpas 299 cells. The quantification results were shown in the right panel.

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