A Cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation

Z.R. Yu, C.G. Wang, M. Wang, Z.P. Li, M.C. Casimiro, M.R. Liu, K.M. Wu, James Whittle, X.M. Ju, T. Hyslop, P. Mccue, R.G. Pestell

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    Abstract

    Decreased expression of specific microRNAs (miRNAs) occurs in human tumors, which suggests a function for miRNAs in tumor suppression. Herein, levels of the miR-17-5p/miR-20a miRNA cluster were inversely correlated to cyclin D1 abundance in human breast tumors and cell lines. MiR-17/20 suppressed breast cancer cell proliferation and tumor colony formation by negatively regulating cyclin D1 translation via a conserved 3′ untranslated region miRNA-binding site, thereby inhibiting serum-induced S phase entry. The cell cycle effect of miR-17/20 was abrogated by cyclin D1 siRNA and in cyclin D1–deficient breast cancer cells. Mammary epithelial cell–targeted cyclin D1 expression induced miR-17-5p and miR-20a expression in vivo, and cyclin D1 bound the miR-17/20 cluster promoter regulatory region. In summary, these studies identify a novel cyclin D1/miR-17/20 regulatory feedback loop through which cyclin D1 induces miR-17-5p/miR-20a. In turn, miR-17/20 limits the proliferative function of cyclin D1, thus linking expression of a specific miRNA cluster to the regulation of oncogenesis.
    Original languageEnglish
    Pages (from-to)509-517
    JournalJournal of Cell Biology
    Volume182
    Issue number3
    DOIs
    Publication statusPublished - 2008

    Fingerprint

    Cyclin D1
    MicroRNAs
    Cell Proliferation
    Breast Neoplasms
    Neoplasms
    Cyclins
    Nucleic Acid Regulatory Sequences
    3' Untranslated Regions
    Tumor Cell Line
    S Phase
    Genetic Promoter Regions
    Small Interfering RNA
    Cell Cycle
    Carcinogenesis
    Breast
    Binding Sites
    Serum

    Cite this

    Yu, Z. R., Wang, C. G., Wang, M., Li, Z. P., Casimiro, M. C., Liu, M. R., ... Pestell, R. G. (2008). A Cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. Journal of Cell Biology, 182(3), 509-517. https://doi.org/10.1083/jcb.200801079
    Yu, Z.R. ; Wang, C.G. ; Wang, M. ; Li, Z.P. ; Casimiro, M.C. ; Liu, M.R. ; Wu, K.M. ; Whittle, James ; Ju, X.M. ; Hyslop, T. ; Mccue, P. ; Pestell, R.G. / A Cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. In: Journal of Cell Biology. 2008 ; Vol. 182, No. 3. pp. 509-517.
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    title = "A Cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation",
    abstract = "Decreased expression of specific microRNAs (miRNAs) occurs in human tumors, which suggests a function for miRNAs in tumor suppression. Herein, levels of the miR-17-5p/miR-20a miRNA cluster were inversely correlated to cyclin D1 abundance in human breast tumors and cell lines. MiR-17/20 suppressed breast cancer cell proliferation and tumor colony formation by negatively regulating cyclin D1 translation via a conserved 3′ untranslated region miRNA-binding site, thereby inhibiting serum-induced S phase entry. The cell cycle effect of miR-17/20 was abrogated by cyclin D1 siRNA and in cyclin D1–deficient breast cancer cells. Mammary epithelial cell–targeted cyclin D1 expression induced miR-17-5p and miR-20a expression in vivo, and cyclin D1 bound the miR-17/20 cluster promoter regulatory region. In summary, these studies identify a novel cyclin D1/miR-17/20 regulatory feedback loop through which cyclin D1 induces miR-17-5p/miR-20a. In turn, miR-17/20 limits the proliferative function of cyclin D1, thus linking expression of a specific miRNA cluster to the regulation of oncogenesis.",
    author = "Z.R. Yu and C.G. Wang and M. Wang and Z.P. Li and M.C. Casimiro and M.R. Liu and K.M. Wu and James Whittle and X.M. Ju and T. Hyslop and P. Mccue and R.G. Pestell",
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    Yu, ZR, Wang, CG, Wang, M, Li, ZP, Casimiro, MC, Liu, MR, Wu, KM, Whittle, J, Ju, XM, Hyslop, T, Mccue, P & Pestell, RG 2008, 'A Cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation' Journal of Cell Biology, vol. 182, no. 3, pp. 509-517. https://doi.org/10.1083/jcb.200801079

    A Cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. / Yu, Z.R.; Wang, C.G.; Wang, M.; Li, Z.P.; Casimiro, M.C.; Liu, M.R.; Wu, K.M.; Whittle, James; Ju, X.M.; Hyslop, T.; Mccue, P.; Pestell, R.G.

    In: Journal of Cell Biology, Vol. 182, No. 3, 2008, p. 509-517.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - A Cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation

    AU - Yu, Z.R.

    AU - Wang, C.G.

    AU - Wang, M.

    AU - Li, Z.P.

    AU - Casimiro, M.C.

    AU - Liu, M.R.

    AU - Wu, K.M.

    AU - Whittle, James

    AU - Ju, X.M.

    AU - Hyslop, T.

    AU - Mccue, P.

    AU - Pestell, R.G.

    PY - 2008

    Y1 - 2008

    N2 - Decreased expression of specific microRNAs (miRNAs) occurs in human tumors, which suggests a function for miRNAs in tumor suppression. Herein, levels of the miR-17-5p/miR-20a miRNA cluster were inversely correlated to cyclin D1 abundance in human breast tumors and cell lines. MiR-17/20 suppressed breast cancer cell proliferation and tumor colony formation by negatively regulating cyclin D1 translation via a conserved 3′ untranslated region miRNA-binding site, thereby inhibiting serum-induced S phase entry. The cell cycle effect of miR-17/20 was abrogated by cyclin D1 siRNA and in cyclin D1–deficient breast cancer cells. Mammary epithelial cell–targeted cyclin D1 expression induced miR-17-5p and miR-20a expression in vivo, and cyclin D1 bound the miR-17/20 cluster promoter regulatory region. In summary, these studies identify a novel cyclin D1/miR-17/20 regulatory feedback loop through which cyclin D1 induces miR-17-5p/miR-20a. In turn, miR-17/20 limits the proliferative function of cyclin D1, thus linking expression of a specific miRNA cluster to the regulation of oncogenesis.

    AB - Decreased expression of specific microRNAs (miRNAs) occurs in human tumors, which suggests a function for miRNAs in tumor suppression. Herein, levels of the miR-17-5p/miR-20a miRNA cluster were inversely correlated to cyclin D1 abundance in human breast tumors and cell lines. MiR-17/20 suppressed breast cancer cell proliferation and tumor colony formation by negatively regulating cyclin D1 translation via a conserved 3′ untranslated region miRNA-binding site, thereby inhibiting serum-induced S phase entry. The cell cycle effect of miR-17/20 was abrogated by cyclin D1 siRNA and in cyclin D1–deficient breast cancer cells. Mammary epithelial cell–targeted cyclin D1 expression induced miR-17-5p and miR-20a expression in vivo, and cyclin D1 bound the miR-17/20 cluster promoter regulatory region. In summary, these studies identify a novel cyclin D1/miR-17/20 regulatory feedback loop through which cyclin D1 induces miR-17-5p/miR-20a. In turn, miR-17/20 limits the proliferative function of cyclin D1, thus linking expression of a specific miRNA cluster to the regulation of oncogenesis.

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    DO - 10.1083/jcb.200801079

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    EP - 517

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    JF - Journal of Cell Biology

    SN - 0021-9525

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    ER -