PDGF induced microRNA alterations in cancer cells

Minghai Shao; Simona Rossi; Bhadrani Chelladurai; Masayoshi Shimizu; Obiageli Ntukogu; Mircea Ivan; George A. Calin; Daniela Matei

doi:10.1093/nar/gkq1305

PDGF induced microRNA alterations in cancer cells

Minghai Shao, Simona Rossi, Bhadrani Chelladurai, Masayoshi Shimizu, Obiageli Ntukogu, Mircea Ivan, George A. Calin, Daniela Matei

Graduate School of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

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.

Original language	English (US)
Pages (from-to)	4035-4047
Number of pages	13
Journal	Nucleic acids research
Volume	39
Issue number	10
DOIs	https://doi.org/10.1093/nar/gkq1305
State	Published - May 2011

ASJC Scopus subject areas

Genetics

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10.1093/nar/gkq1305

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title = "PDGF induced microRNA alterations in cancer cells",

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.",

author = "Minghai Shao and Simona Rossi and Bhadrani Chelladurai and Masayoshi Shimizu and Obiageli Ntukogu and Mircea Ivan and Calin, {George A.} and Daniela Matei",

note = "Funding Information: American Cancer Society (ACS), Mentored Research Scholar Grant (MRSG#107613 to D.M.); research funds (Fellow of the UTM to G.A.C.); D. Anderson Research Trust and Research Scholar of the UT System Regents; Ladjevardian Regents Research Scholar Fund. Funding for open access charge: American Concern Society.",

year = "2011",

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doi = "10.1093/nar/gkq1305",

language = "English (US)",

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AU - Shao, Minghai

AU - Rossi, Simona

AU - Chelladurai, Bhadrani

AU - Shimizu, Masayoshi

AU - Ntukogu, Obiageli

AU - Ivan, Mircea

AU - Calin, George A.

AU - Matei, Daniela

N1 - Funding Information: American Cancer Society (ACS), Mentored Research Scholar Grant (MRSG#107613 to D.M.); research funds (Fellow of the UTM to G.A.C.); D. Anderson Research Trust and Research Scholar of the UT System Regents; Ladjevardian Regents Research Scholar Fund. Funding for open access charge: American Concern Society.

PY - 2011/5

Y1 - 2011/5

N2 - 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.

AB - 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 induced microRNA alterations in cancer cells

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