title: siRNA-Mediated SBF2 Silencing May Inhibit Pancreatic Cancer Cells via Attenuation of the TGF-β Signaling Pathway.
abstract: OBJECTIVE
  To investigate the effects of small-interfering RNA (siRNA)-mediated silencing of SET binding factor 2 (SBF2) on pancreatic cancer cells and its underlying molecular mechanisms.
  
  
  METHODS
  Five siRNAs, namely, siRNA-1, siRNA-2, siRNA-3, siRNA-4, and siRNA-5, were designed to silence SBF2 in pancreatic cancer PANC-1 cells. The relative expression levels of SBF2 after siRNA-mediated SBF2 silencing were detected by real-time polymerase chain reaction (RT-PCR). The inhibition and apoptosis of cells were detected by methyl thiazolyl tetrazolium and flow cytometry, respectively. The protein concentrations of SBF2, SMAD-2, phosphorylated-SMAD-2 (p-SMAD-2), SMAD-3, p-SMAD-3, and SMAD-7 were also measured via Western blot.
  
  
  RESULTS
  The relative expression levels of SBF2 in the siRNA-mediated SBF2-silenced groups decreased significantly (P < .05), and the proliferation of PANC-1 cells was significantly inhibited (P < .01) after SBF2 silencing using the 5 siRNAs. The relative expression level of SBF2 was the lowest (0.52 ± 0.05) and the cell inhibition rate was the highest (36.7 ± 4.0%) in the SBF2-silenced PANC-1 cells using siRNA-3 compared to the 5 siRNA-mediated SBF2-silenced groups. The cell apoptosis rate in the siRNA-3 transfection group was significantly higher than that in the control group (P < .05). The concentrations of p-SMAD-2 and p-SMAD-3 were reduced, while the concentrations of SMAD-2, SMAD-3, and SMAD-7 were increased in the siRNA-3-mediated SBF2-silenced PANC-1 cells.
  
  
  CONCLUSIONS
  SiRNA-mediated SBF2 silencing could significantly inhibit the proliferation and promote the apoptosis of pancreatic cancer cells possibly via attenuation of transforming growth factor β/SMAD signaling pathway. And SBF2 silencing can be a potential approach for treatment of pancreatic cancer.
authors.affiliation: Department of General Surgery, the First Hospital of China Medical University, Shenyang, China long_ljin@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Long
authors.affiliation: Department of General Surgery, the First Hospital of China Medical University, Shenyang, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of General Surgery, the First Hospital of China Medical University, Shenyang, China.
authors.forename: Xingda
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of General Surgery, the First Hospital of China Medical University, Shenyang, China.
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of General Surgery, the First Hospital of China Medical University, Shenyang, China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Ge
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D010190:Pancreatic Neoplasms; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C475072:SBF2 protein, human
keywords: SBF2 gene; cell apoptosis; cell proliferation; inhibition; pancreatic cancer