title: MicroRNA-335 inhibits tumor reinitiation and is silenced through genetic and epigenetic mechanisms in human breast cancer.
abstract: Post-transcriptional regulators have emerged as robust effectors of metastasis and display deregulated expression through unknown mechanisms. Here, we reveal that the human microRNA-335 locus undergoes genetic deletion and epigenetic promoter hypermethylation in every metastatic derivative obtained from independent patients' malignant cell populations. Genetic deletion of miR-335 is a common event in human breast cancer, is enriched for in breast cancer metastases, and also correlates with ovarian cancer recurrence. We furthermore identify miR-335 as a robust inhibitor of tumor reinitiation. We thus implicate the miR-335 locus on 7q32.2 as the first selective metastasis suppressor and tumor initiation suppressor locus in human breast cancer.
authors.affiliation: Laboratory of Systems Cancer Biology, Rockefeller University, New York, NY 10065, USA.
authors.forename: Kim J
authors.initials: KJ
authors.lastname: Png
authors.forename: Mitsukuni
authors.initials: M
authors.lastname: Yoshida
authors.forename: Xiang H-F
authors.initials: XH
authors.lastname: Zhang
authors.forename: Weiping
authors.initials: W
authors.lastname: Shu
authors.forename: Hyeseung
authors.initials: H
authors.lastname: Lee
authors.forename: Andreas
authors.initials: A
authors.lastname: Rimner
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Chan
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Comen
authors.forename: Viktor P
authors.initials: VP
authors.lastname: Andrade
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Tari A
authors.initials: TA
authors.lastname: King
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: James
authors.initials: J
authors.lastname: Hicks
authors.forename: Joan
authors.initials: J
authors.lastname: Massagué
authors.forename: Sohail F
authors.initials: SF
authors.lastname: Tavazoie
mesh_terms: D001943:Breast Neoplasms / Q000503:physiopathology*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D017353:Gene Deletion; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000503:physiopathology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference
chemical_list: C556347:MIRN335 microRNA, human; D035683:MicroRNAs