title: miR424-5p functions as an anti-oncogene in cervical cancer cell growth by targeting KDM5B via the Notch signaling pathway.
abstract: OBJECTIVE
  Aberrant expression of miRNAs exert the critical roles in carcinogenesis, including cervical cancer. Recent study corroborated the down-regulation of miR424-5p in uterine cervix adenocarcinoma. This research aimed to investigate the function and underlying mechanisms of miR424-5p in cervical cancer cell growth.
  
  
  METHODS
  Tissues samples were collected from patients with cervical cancer and healthy control. The expression levels of miR424-5p were determined by qRT-PCR. After transfection with miR424-5p mimics or inhibitor, cervical cancer cell proliferation and apoptosis were evaluated by WST-1 and flow cytometry assay, respectively. The underlying mechanism involved in aforementioned processes was also explored.
  
  
  RESULTS
  Expression of miR424-5p was notably decreased in cervical cancer tissues and cells. Overexpression of miR424-5p restrained cell proliferation and promoted cell apoptosis, but with little function in miR424-5p inhibitor-treated groups. Furthermore, KDM5B was identified as a direct target of miR424-5p as the evidence that miR-424-5p inhibited KDM5B expression and luciferase activity of KDM5B 3'-UTR. Here, KDM5B elevation majorly reversed miR424-5p-triggered inhibition in cell proliferation and increase in cell apoptosis. Moreover, silencing KDM5B expression also restrained cell growth. Additionally, miR424-5p overexpression inhibited the expression of Notch1 and Notch2, which was obviously rescued after KDM5B up-regulation. Simultaneously, blocking KDM5B also attenuated the activation of Notch pathway. Importantly, treatment with Notch agonist Jagged1 antagonized miR424-5p-mediated suppression on cell growth.
  
  
  CONCLUSIONS
  This research suggests that miR424-5p may act as a novel anti-oncogene in cervical cancer by blocking cell growth through targeting KDM5B-Notch pathway. Accordingly, our study will support a promising therapeutic strategy against cervical carcinoma.
authors.affiliation: Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: An
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.
authors.forename: Rui-Xia
authors.initials: RX
authors.lastname: Guo
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.
authors.forename: Yu-Huan
authors.initials: YH
authors.lastname: Qiao
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.
authors.forename: Liu-Xia
authors.initials: LX
authors.lastname: Li
authors.affiliation: Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China. Electronic address: xiaolanzhaoxlz@163.com.
authors.forename: Xian-Lan
authors.initials: XL
authors.lastname: Zhao
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D055785:Gene Knockdown Techniques; D016147:Genes, Tumor Suppressor; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D051880:Receptors, Notch / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics*; D015398:Signal Transduction; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: C554214:MIRN424 microrna, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C119611:KDM5B protein, human
keywords: Cervical cancer; Jagged1; KDM5B; MiR424-5p