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PDGF induced microRNA alterations in cancer cells.

Shao M, Rossi S, Chelladurai B, Shimizu M, Ntukogu O, Ivan M, Calin GA, Matei D - Nucleic Acids Res. (2011)

Bottom Line: Here, we show by using microRNA (miR) arrays that PDGFs regulate the expression and function of miRs in glioblastoma and ovarian cancer cells.We demonstrate that PDGF regulates expression of some of its known targets (e.g. cyclin D1) through miR alterations and identify the epidermal growth factor receptor (EGFR) as a new PDGF-BB target.We show that its expression and function are repressed by PDGF-induced miR-146b and that mir-146b and EGFR correlate inversely in human glioblastomas.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Indiana University School of Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

ABSTRACT
Platelet derived growth factor (PDGF) regulates gene transcription by binding to specific receptors. PDGF plays a critical role in oncogenesis in brain and other tumors, regulates angiogenesis, and remodels the stroma in physiologic conditions. Here, we show by using microRNA (miR) arrays that PDGFs regulate the expression and function of miRs in glioblastoma and ovarian cancer cells. The two PDGF ligands AA and BB affect expression of several miRs in ligand-specific manner; the most robust changes consisting of let-7d repression by PDGF-AA and miR-146b induction by PDGF-BB. Induction of miR-146b by PDGF-BB is modulated via MAPK-dependent induction of c-fos. We demonstrate that PDGF regulates expression of some of its known targets (e.g. cyclin D1) through miR alterations and identify the epidermal growth factor receptor (EGFR) as a new PDGF-BB target. We show that its expression and function are repressed by PDGF-induced miR-146b and that mir-146b and EGFR correlate inversely in human glioblastomas. We propose that PDGF-regulated gene transcription involves alterations in non-coding RNAs and provide evidence for a miR-dependent feedback mechanism balancing growth factor receptor signaling in cancer cells.

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PDGF BB up-regulates miR-146b. (A) qPCR quantifies miR-146b in U118, U87-MG, C272/hTert/E7 and SH-SY5Y after PDGF-BB treatment. (B) qPCR quantifies miR-146b in WI38 fibroblasts after PDGF-BB treatment. (C) qPCR quantifies miR-146b in C272/hTert/E7 cells in response to PDGF-AA, PDGF-BB, VEGF and EGF. (D) qPCR quantifies miR-146b in C272hTert/E7 cells treated with PDGF-BB and PD98059, LY294002 and imatinib mesylate. RNU49 was used as control for all qPCR reactions.
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Figure 3: PDGF BB up-regulates miR-146b. (A) qPCR quantifies miR-146b in U118, U87-MG, C272/hTert/E7 and SH-SY5Y after PDGF-BB treatment. (B) qPCR quantifies miR-146b in WI38 fibroblasts after PDGF-BB treatment. (C) qPCR quantifies miR-146b in C272/hTert/E7 cells in response to PDGF-AA, PDGF-BB, VEGF and EGF. (D) qPCR quantifies miR-146b in C272hTert/E7 cells treated with PDGF-BB and PD98059, LY294002 and imatinib mesylate. RNU49 was used as control for all qPCR reactions.

Mentions: Next, we focused on the effects of PDGF-BB and showed by qPCR that miR-146b was induced by up to 2-fold in U118MG, U87MG, C272hTert/E7 and SH-SY5Y cells within 6–16 h (Figure 3A). The induction in miR-146b expression was sustained (up to 24 h) in the cancer cells tested here. Lesser induction of miR-146b (∼30%) was observed in non-transformed WI38 fibroblasts stimulated with PDGF-BB (Figure 3B). To test the specificity of this miR’s response to individual growth factors, C272/hTert/E7 cells were treated with PDGF-AA, PDGF-BB, EGF and VEGF and miR-146b was quantified. A 2-fold increase in miR-146b expression level was noted in response to PDGF-BB, while PDGF-AA, EGF and VEGF did not induce significant variation of miR-146b levels (Figure 3C).Figure 3.


PDGF induced microRNA alterations in cancer cells.

Shao M, Rossi S, Chelladurai B, Shimizu M, Ntukogu O, Ivan M, Calin GA, Matei D - Nucleic Acids Res. (2011)

PDGF BB up-regulates miR-146b. (A) qPCR quantifies miR-146b in U118, U87-MG, C272/hTert/E7 and SH-SY5Y after PDGF-BB treatment. (B) qPCR quantifies miR-146b in WI38 fibroblasts after PDGF-BB treatment. (C) qPCR quantifies miR-146b in C272/hTert/E7 cells in response to PDGF-AA, PDGF-BB, VEGF and EGF. (D) qPCR quantifies miR-146b in C272hTert/E7 cells treated with PDGF-BB and PD98059, LY294002 and imatinib mesylate. RNU49 was used as control for all qPCR reactions.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 3: PDGF BB up-regulates miR-146b. (A) qPCR quantifies miR-146b in U118, U87-MG, C272/hTert/E7 and SH-SY5Y after PDGF-BB treatment. (B) qPCR quantifies miR-146b in WI38 fibroblasts after PDGF-BB treatment. (C) qPCR quantifies miR-146b in C272/hTert/E7 cells in response to PDGF-AA, PDGF-BB, VEGF and EGF. (D) qPCR quantifies miR-146b in C272hTert/E7 cells treated with PDGF-BB and PD98059, LY294002 and imatinib mesylate. RNU49 was used as control for all qPCR reactions.
Mentions: Next, we focused on the effects of PDGF-BB and showed by qPCR that miR-146b was induced by up to 2-fold in U118MG, U87MG, C272hTert/E7 and SH-SY5Y cells within 6–16 h (Figure 3A). The induction in miR-146b expression was sustained (up to 24 h) in the cancer cells tested here. Lesser induction of miR-146b (∼30%) was observed in non-transformed WI38 fibroblasts stimulated with PDGF-BB (Figure 3B). To test the specificity of this miR’s response to individual growth factors, C272/hTert/E7 cells were treated with PDGF-AA, PDGF-BB, EGF and VEGF and miR-146b was quantified. A 2-fold increase in miR-146b expression level was noted in response to PDGF-BB, while PDGF-AA, EGF and VEGF did not induce significant variation of miR-146b levels (Figure 3C).Figure 3.

Bottom Line: Here, we show by using microRNA (miR) arrays that PDGFs regulate the expression and function of miRs in glioblastoma and ovarian cancer cells.We demonstrate that PDGF regulates expression of some of its known targets (e.g. cyclin D1) through miR alterations and identify the epidermal growth factor receptor (EGFR) as a new PDGF-BB target.We show that its expression and function are repressed by PDGF-induced miR-146b and that mir-146b and EGFR correlate inversely in human glioblastomas.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Indiana University School of Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

ABSTRACT
Platelet derived growth factor (PDGF) regulates gene transcription by binding to specific receptors. PDGF plays a critical role in oncogenesis in brain and other tumors, regulates angiogenesis, and remodels the stroma in physiologic conditions. Here, we show by using microRNA (miR) arrays that PDGFs regulate the expression and function of miRs in glioblastoma and ovarian cancer cells. The two PDGF ligands AA and BB affect expression of several miRs in ligand-specific manner; the most robust changes consisting of let-7d repression by PDGF-AA and miR-146b induction by PDGF-BB. Induction of miR-146b by PDGF-BB is modulated via MAPK-dependent induction of c-fos. We demonstrate that PDGF regulates expression of some of its known targets (e.g. cyclin D1) through miR alterations and identify the epidermal growth factor receptor (EGFR) as a new PDGF-BB target. We show that its expression and function are repressed by PDGF-induced miR-146b and that mir-146b and EGFR correlate inversely in human glioblastomas. We propose that PDGF-regulated gene transcription involves alterations in non-coding RNAs and provide evidence for a miR-dependent feedback mechanism balancing growth factor receptor signaling in cancer cells.

Show MeSH
Related in: MedlinePlus