title: MicroRNA-25 regulates small cell lung cancer cell development and cell cycle through cyclin E2.
abstract: OBJECTIVE
  We intended to examine the underlying mechanism of microRNA-25 (miR-25) in regulating small cell lung cancer (SCLC).
  
  
  METHODS
  The miR-25 expression was measured by quantitative RT-PCR (qRT-PCR) in 5 SCLC cell lines and 9 human SCLC tissues. In SCLC cell line H510A cells, endogenous miR-25 was downregulated by stable transfection of antisense oligonucleotide of miR-25 (miR-25-as). Then the effects of miR-25 downregulation on SCLC growth, invasion and chemoresistance were assessed by MTT, migration and cisplatin assays, respectively. Furthermore, the effects of miR-25 downregulation on cancer cell cycle arrest, production of cell cycle proteins cyclin E2 and CDK2 were examined by cell cycle assay, western blot and luciferase assays, respectively. Finally, cyclin E2 was over-expressed in H510A cells to investigate its effect on miR-25 mediated SCLC regulation.
  
  
  RESULTS
  In both SCLC cells and human SCLC tumor tissues, miR-25 was overexpressed. Down-regulation of miR-25 in H510A cells significantly reduced cancer cell growth, invasive capability and resistance to cisplatin. Also, it induced G1 cell cycle arrest and downregulated cell cycle related proteins cyclin E2 and CDK2. Luciferase assay demonstrated cyclin E2 was directly targeted by miR-25. Overexpression of cyclin E2 in H510A cells reversed the cell cycle arrest and restored invasive capability impaired by miR-25 downregulation.
  
  
  CONCLUSIONS
  Our study shows miR-25 is overexpressed in SCLC and acting as oncogenic regulator by regulating cyclin E2.
authors.affiliation: Department of General Thoracic Surgery, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces Tianjin 300162, China.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of General Thoracic Surgery, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces Tianjin 300162, China.
authors.forename: Juntao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of General Thoracic Surgery, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces Tianjin 300162, China.
authors.forename: Changlei
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of General Thoracic Surgery, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces Tianjin 300162, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of General Thoracic Surgery, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces Tianjin 300162, China.
authors.forename: Youguo
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of General Thoracic Surgery, Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces Tianjin 300162, China.
authors.forename: Min
authors.initials: M
authors.lastname: Guo
mesh_terms: D002453:Cell Cycle / Q000502:physiology*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016213:Cyclins / Q000378:metabolism*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C503688:CCNE2 protein, human; D016213:Cyclins; C543351:MIRN25 microRNA, human; D035683:MicroRNAs
keywords: CDK2; SCLC; cyclin E2; miR-25