title: Tumor suppressor role of microRNA-1296 in triple-negative breast cancer.
abstract: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis, which lacks effective targeted therapies. There is an urgent need to better understand the underlying molecular mechanisms of TNBC aggressiveness and identify novel, efficient targets for therapeutic intervention.
  
  
  METHODS
  miRNA qRT-PCR was used to determine the expression of miR-1296 in cell lines. The miR-1296 overexpression effects in TNBC cell lines were investigated using assays of colony formation, cell cycle and apoptosis. Immunoblotting was performed to determine the expression of the miR-1296 target protein, and luciferase assays were performed to confirm the target of miR-1296 action.
  
  
  RESULTS
  miR-1296 expression was significantly suppressed in TNBC cell lines and tissues samples. Overexpression of miR-1296 significantly suppressed cell proliferation of two TNBC cell lines when compared to control miRNA-expressing cells. A significant decrease in the S-phase of the cell cycle was observed following miR-1296 overexpression, accompanied by induction of apoptosis in TNBC cells. Cyclin D1 (CCND1) was identified as a target of miR-1296 action. miR-1296 overexpression significantly suppressed the luciferase activity of reporter plasmid containing the 3'UTR of CCND1 and protein expression levels of CCND1 in TNBC cells. The effects of miR-1296 overexpression on TNBC cell growth were reversed by CCND1 overexpression. miR-1296 expression sensitized TNBC cells to cisplatin treatment.
  
  
  CONCLUSIONS
  Our results demonstrate a novel tumor suppressor role for miR-1296 in triple-negative breast cancer cell lines, identify CCND1 as its target of action, and demonstrate a potential role for miR-1296 in sensitizing breast cancer cells to cisplatin.
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
authors.forename: Binh
authors.initials: B
authors.lastname: Phan
authors.affiliation: Department of Urology, Veterans Affairs Medical Center and University of California San Francisco, San Francisco, CA 94121, USA.
authors.forename: Shahana
authors.initials: S
authors.lastname: Majid
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ursu
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
authors.forename: David
authors.initials: D
authors.lastname: de Semir
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nosrati
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bezrookove
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kashani-Sabet
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
authors.forename: Altaf A
authors.initials: AA
authors.lastname: Dar
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D015151:Immunoblotting; D035683:MicroRNAs / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C530104:CCND1 protein, human; C000621896:MIRN-1296 microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1; D002945:Cisplatin
keywords: apoptosis; cyclin D1; microRNA-1296; triple negative breast cancer; tumor suppressor