sepantronium and Uterine-Cervical-Neoplasms

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.

Topics: 3' Untranslated Regions; Animals; Blotting, Western; Cell Line, Tumor; Cell Movement; Cell Survival; Dose-Response Relationship, Drug; Female; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Imidazoles; Inhibitor of Apoptosis Proteins; Kaplan-Meier Estimate; Lymphatic Metastasis; Mice, SCID; MicroRNAs; Middle Aged; Naphthoquinones; Neoplasm Invasiveness; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Survivin; Uterine Cervical Neoplasms; Xenograft Model Antitumor Assays