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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Yu, Z; Wang, C; Wang, M; Li, Z; Casimiro, MC; Liu, M; Wu, K; Whittle, J; Ju, X; Hyslop, T; McCue, P; Pestell, RG

Published Date

  • August 11, 2008

Published In

Volume / Issue

  • 182 / 3

Start / End Page

  • 509 - 517

PubMed ID

  • 18695042

Pubmed Central ID

  • 18695042

Electronic International Standard Serial Number (EISSN)

  • 1540-8140

Digital Object Identifier (DOI)

  • 10.1083/jcb.200801079

Language

  • eng

Conference Location

  • United States