title: Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration.
abstract: The progression of cancer to metastatic disease is a major cause of death. We identified miR-708 being transcriptionally repressed by polycomb repressor complex 2-induced H3K27 trimethylation in metastatic breast cancer. miR-708 targets the endoplasmic reticulum protein neuronatin to decrease intracellular calcium level, resulting in reduction of activation of ERK and FAK, decreased cell migration, and impaired metastases. Ectopic expression of neuronatin refractory to suppression by miR-708 rescued cell migration and metastasis defects. In patients with breast cancer, miR-708 expression was decreased in lymph node and distal metastases, suggesting a metastasis-suppressive role. Our findings uncover a mechanistic role for miR-708 in metastasis and provide a rationale for developing miR-708 as a therapeutic agent against metastatic breast cancer.
authors: Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.
authors: Seongho
authors: S
authors: Ryu
authors: Kevin
authors: K
authors: McDonnell
authors: Hyejin
authors: H
authors: Choi
authors: Dingcheng
authors: D
authors: Gao
authors: Mary
authors: M
authors: Hahn
authors: Natasha
authors: N
authors: Joshi
authors: Sun-Mi
authors: SM
authors: Park
authors: Raul
authors: R
authors: Catena
authors: Yoonkyung
authors: Y
authors: Do
authors: Jacqueline
authors: J
authors: Brazin
authors: Linda T
authors: LT
authors: Vahdat
authors: Randi B
authors: RB
authors: Silver
authors: Vivek
authors: V
authors: Mittal
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002465:Cell Movement; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D020935:MAP Kinase Signaling System / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D063146:Polycomb-Group Proteins / Q000502:physiology*
chemical_list: C568528:MIRN708 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C490237:NNAT protein, human; D009419:Nerve Tissue Proteins; D063146:Polycomb-Group Proteins; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium