title: miR-17-5p/20a are important markers for gastric cancer and murine double minute 2 participates in their functional regulation.
abstract: OBJECTIVE
  To investigate the potential roles and mechanisms of miR-17-5p/20a in human gastric cancer development and progression.
  
  
  METHODS
  Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine miR-17-5p/20a expression profiles in 110 gastric cancer tissues. microRNAs' (miRNAs) mimics and inhibitors were used to reveal their function in gastric cancer. Antagomirs were applied to treating gastric cancer cell derived xenograft in vivo. Western blot and luciferase assays were performed to uncover the targets and mechanisms of miR-17-5p/20a.
  
  
  RESULTS
  miR-17-5p/20a levels were upregulated in human gastric cancer tissues. Overexpression of miR-17-5p/20a promoted gastric cancer cell cycle progression and inhibited cell apoptosis, whereas knockdown of miR-17-5p/20a resulted in cell cycle arrest and increased apoptosis. p21 and tumour protein p53-induced nuclear protein 1 (TP53INP1) were validated as the targets of miR-17-5p/20a. Antagomirs against miR-17-5p/20a significantly inhibited gastric cancer growth via upregulation of p21 and TP53INP1 in a mouse xenograft model. The negative relationship between miR-17-5p/20a and TP53INP1 was observed in patient gastric cancer tissues. Murine double minute 2 (MDM2) was found to be involved in miRNA regulation and function. Targeted inhibition of MDM2 in a miRNA mimic-transfected gastric cancer cell line abolished miR-17-5p/20a function and inhibition of p21 expression. MDM2 restoration by pCMV-MDM2 rescued the functionality.
  
  
  CONCLUSIONS
  Our findings indicate that miR-17-5p/20a promote gastric cancer cell proliferation and inhibit cell apoptosis via post-transcriptional modulation of p21 and TP53INP1. They may be promising therapeutic markers for gastric cancer. MDM2 contributes to miR-17-5p/20a function and inhibition of p21 in gastric cancer, and may be a novel mechanism underlying the oncogenic roles of miR-17-5p/20a.
authors: School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors: Mei
authors: M
authors: Wang
authors: Hongbing
authors: H
authors: Gu
authors: Hui
authors: H
authors: Qian
authors: Wei
authors: W
authors: Zhu
authors: Chonghui
authors: C
authors: Zhao
authors: Xu
authors: X
authors: Zhang
authors: Yang
authors: Y
authors: Tao
authors: Ling
authors: L
authors: Zhang
authors: Wenrong
authors: W
authors: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009841:Oligonucleotides / Q000235:genetics / Q000494:pharmacology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006360:Heat-Shock Proteins; C524941:MIRN17 microRNA, human; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; C543614:Mirn17 microRNA, mouse; C532375:Mirn20 microRNA, mouse; D009841:Oligonucleotides; C429767:TP53INP1 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2