title: Inhibition of polypyrimidine tract-binding protein 3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5- fluorouracil in gastric cancer cells.
abstract: BACKGROUND
  Human polypyrimidine tract binding protein 3 (PTBP3) was first discovered in 1999 and has been well characterised as a differentiation regulator. However, its role in human cancer has rarely been reported. Our previous study revealed increased PTBP3 protein level in gastric cancer tissues. Downregulation of PTBP3 suppressed the proliferation and differentiation of gastric cancer cells in vivo.
  
  
  METHODS
  PTBP3 mRNA levels in human gastric cancer and adjuvant non-tumour tissues were detected. Apoptosis and 5-FU effect were determined in PTBP3-silenced gastric cancer cells. Underlying molecular mechanisms were investigated.
  
  
  RESULTS
  MRNA expression of PTBP3 was upregulated in gastric cancer tissues, especially in those at an advanced stage. PTBP3 silencing led to apoptosis, under which modulation of PTB and thereby switch of Bcl-x pre-mRNA splicing pattern might be an important mechanism. Further research found that inhibition of PTBP3 expression enhanced the chemosensitivity of gastric cancer cells towards 5-FU treatment. This was mediated by reduced expression of histone deacetylase 6 (HDAC6), which further inhibited the phosphorylation of Akt and the expression of thymidylate synthase (TYMS), the critical determinant of 5-FU cytotoxicity.
  
  
  CONCLUSIONS
  PTBP3 might serve as a biomarker of gastric cancer or potential target for anti-cancer therapy.
authors.affiliation: State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, PO Box 268, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, PO Box 268, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, PO Box 268, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, PO Box 268, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Cen
authors.initials: C
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, PO Box 268, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Shengchao
authors.initials: S
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, PO Box 268, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, 301 Yanchang Road, Shanghai 200072, China.
authors.forename: Jiyu
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai 200032, China.
authors.forename: Aiguang
authors.initials: A
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, PO Box 268, 130 Meilong Road, Shanghai 200237, China.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D038941:Polypyrimidine Tract-Binding Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C118823:PTBP3 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D038941:Polypyrimidine Tract-Binding Protein; D005472:Fluorouracil