title: MicroRNA-449a inhibits proliferation and induces apoptosis by directly repressing E2F3 in gastric cancer.
abstract: BACKGROUND
  MicroRNA-449a is a tumor suppressor that is down-regulated in multiple tumors types. However, the role of miR-449a in gastric cancer (GC) remains largely unknown.
  
  
  METHODS
  MiR-449a expression was up-regulated using miR-449a mimics, and the role of miR-449a in GC was assessed using cell viability and apoptosis assays. miR-449a target genes were confirmed using luciferase activity, RT-PCR and western blot assays.
  
  
  RESULTS
  miR-449a was downregulated in gastric cancer cell lines and gastric cancer tissues. Restoration of miR-449a expression inhibited gastric cancer cell proliferation and colony formation. Significant G0/G1 arrest was observed in gastric cancer cells transfected with miR-449a mimics. Furthermore, combination therapy with miR-449a with cisplatin displayed greater anti-tumor effects than treatment with cisplatin alone. We also identified E2F3 (E2F transcription factor 3), an important transcription factor involved in the proliferation and metastasis of tumor cells, as a direct target gene of miR-449a. Furthermore, silencing E2F3 elicits similar a repressive effect as overexpression of miR-449a in gastric cancer cells, and E2F3 overexpression rescued the repressing effects of miR-449a mimics.
  
  
  CONCLUSIONS
  This study indicates that the miR-449a/E2F3 axis plays an important role in proliferation and apoptosis in gastric cancer. Therefore, miR-449a represents a novel target for gastric cancer therapy.
authors: Department of Clinical Laboratory, Wujiang first people's hospital Affiliated Nantong University, Suzhou, People's Republic of China.
authors: Xiaoping
authors: X
authors: Li
authors: Hong
authors: H
authors: Li
authors: Rui
authors: R
authors: Zhang
authors: Jing
authors: J
authors: Liu
authors: Jun
authors: J
authors: Liu
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D050699:E2F3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; C544530:MIRN449 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D002945:Cisplatin