title: MiR-34a Inhibits Viability and Invasion of Human Papillomavirus-Positive Cervical Cancer Cells by Targeting E2F3 and Regulating Survivin.
abstract: OBJECTIVE
  Previous studies confirmed that high-risk human papillomavirus (HR-HPV) infection is a risk factor of cervical cancer, and the infection was associated with significantly reduced miR-34a expression during carcinogenesis. However, the downstream targets of miR-34a and their roles are still not well understood. This study explored the regulative role of miR-34a on E2F3 and survivin expression and the viability and invasion of HPV-positive cervical cancer cells.
  
  
  METHODS
  MiR-34a and survivin expression in 56 cases of HR-HPV-positive patients, 28 cases of HR-HPV-negative patients, and 28 normal cases without HR-HPV infections were measured. Human papillomavirus-18-positive HeLa cervical cancer cells and HPV-16-positive SiHa cells were used to explore the effect of miR-34a on cell viability and invasion. The molecular target of miR-34a was also explored in cervical cancer cells.
  
  
  RESULTS
  The results showed that miR-34a overexpression could inhibit HPV-positive cancer cell viability, whereas its downregulation promoted cell viability. E2F3 is a direct target of miR-34a in HPV-positive cervical cancer cells. By targeting E2F3, miR-34a could regulate the expression of survivin. Thus, through regulating E2F3 and survivin, miR-34a could reduce the viability and invasion of HPV-positive cervical cancer cells.
  
  
  CONCLUSIONS
  This study confirmed a novel miR-34a-E2F3-survivin axis in the tumor suppressor role of miR-34a in cervical cancer.
authors: *Department of Oncology, Binzhou Medical University Hospital; †Department of Obstetrics and Gynecology, Binzhou People's Hospital; and ‡Department of Obstetrics and Gynecology, Zouping Maternal and Child Health-Care Hospital, Shandong, China.
authors: Dianzhong
authors: D
authors: Geng
authors: Xiaohua
authors: X
authors: Song
authors: Fangling
authors: F
authors: Ning
authors: Qianhua
authors: Q
authors: Song
authors: Honghua
authors: H
authors: Yin
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D015153:Blotting, Western; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D050699:E2F3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052162:Human papillomavirus 16 / Q000235:genetics; D052161:Human papillomavirus 18 / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000821:virology
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; D051034:Inhibitor of Apoptosis Proteins; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D000077022:Survivin