title: The microRNA-218~Survivin axis regulates migration, invasion, and lymph node metastasis in cervical cancer.
abstract: Cervical cancer is the third most common cancer in women worldwide. In the present study, global microRNA profiling for 79 cervical cancer patient samples led to the identification of miR-218 down-regulation in cervical cancer tissues compared to normal cervical tissues. Lower miR-218 expression was associated significantly with worse overall survival (OS), disease-free survival (DFS), and pelvic/aortic lymph node recurrence. In vitro, miR-218 over-expression decreased clonogenicity, migration, and invasion. Survivin (BIRC5) was subsequently identified as an important cervical cancer target of miR-218 using in silico prediction, mRNA profiling, and quantitative real-time PCR (qRT-PCR). Concordant with miR-218 over-expression, survivin knockdown by siRNA decreased clonogenicity, migration, and invasion. YM155, a small molecule survivin inhibitor, significantly suppressed tumor growth and lymph node metastasis in vivo. Our findings demonstrate that the miR-218~survivin axis inhibits cervical cancer progression by regulating clonogenicity, migration, and invasion, and suggest that the inhibition of survivin could be a potential therapeutic strategy to improve outcome in this disease.
authors.affiliation: Ontario Cancer Institute, University Health Network (UHN), Toronto, Ontario, Canada.
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Kogo
authors.affiliation: Ontario Cancer Institute, University Health Network (UHN), Toronto, Ontario, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: How
authors.affiliation: Ontario Cancer Institute, University Health Network (UHN), Toronto, Ontario, Canada.
authors.forename: Naz
authors.initials: N
authors.lastname: Chaudary
authors.affiliation: Ontario Cancer Institute, University Health Network (UHN), Toronto, Ontario, Canada.
authors.forename: Jeff
authors.initials: J
authors.lastname: Bruce
authors.affiliation: Ontario Cancer Institute, University Health Network (UHN), Toronto, Ontario, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Ontario Cancer Institute, University Health Network (UHN), Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.|Department of Radiation Oncology, University of Toronto, Toronto, Canada.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hill
authors.affiliation: Ontario Cancer Institute, University Health Network (UHN), Toronto, Ontario, Canada.
authors.forename: Payam
authors.initials: P
authors.lastname: Zahedi
authors.affiliation: Ontario Cancer Institute, University Health Network (UHN), Toronto, Ontario, Canada.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Yip
authors.affiliation: Ontario Cancer Institute, University Health Network (UHN), Toronto, Ontario, Canada.Department of Medical Biophysics, University of Toronto, Toronto, Canada.Department of Radiation Oncology, University of Toronto, Toronto, Canada.Department of Radiation Oncology, Princess Margaret Cancer Centre, UHN, Toronto, Canada.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009285:Naphthoquinones / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; C107489:BIRC5 protein, human; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; D009285:Naphthoquinones; D000077022:Survivin; C523798:sepantronium