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.
authors.affiliation: Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Zuoren
authors.initials: Z
authors.lastname: Yu
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Li
authors.forename: Mathew C
authors.initials: MC
authors.lastname: Casimiro
authors.forename: Manran
authors.initials: M
authors.lastname: Liu
authors.forename: Kongming
authors.initials: K
authors.lastname: Wu
authors.forename: James
authors.initials: J
authors.lastname: Whittle
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Ju
authors.forename: Terry
authors.initials: T
authors.lastname: Hyslop
authors.forename: Peter
authors.initials: P
authors.lastname: McCue
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017124:Conserved Sequence; D019938:Cyclin D1 / Q000235:genetics*; D015536:Down-Regulation; D025461:Feedback, Physiological; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D019938:Cyclin D1