title: microRNA-218 promotes gemcitabine sensitivity in human pancreatic cancer cells by regulating HMGB1 expression.
abstract: OBJECTIVE
  The purpose of this study was to examine the effect of gemcitabine (GEM) on microRNA-218 (miR-218) expression in human pancreatic cancer cells.
  
  
  METHODS
  Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to examine the differences in miR-218 expression between the GEM-sensitive BxPC-3 pancreatic cancer cells and GEM-resistant PANC-1 cells. The effect of GEM on the expression of miR-218 in PANC-1 cells was also investigated. PANC-1 cells were transfected either with HMGB1 siRNA to knock down the expression of HMGB1 or with the recombinant HMGB1 expression vector (pcDNA3.1-HMGB1) to overexpress HMGB1. The effect of ectopic expression of HMGB1 on the apoptosis of miR-218-transfected and GEM-treated PANC-1 cells was examined by flow cytometric analysis.
  
  
  RESULTS
  The miR-218 expression level was lower in GEM-resistant PANC-1 cells compared to GEM-sensitive BxPC-3 cells (P<0.05). The percentage of apoptotic PANC-1 cells was significantly increased in the miR-218 mimic + GEM group compared to the mimic ctrl + GEM group and the normal control group (P<0.01). The HMGB1 expression level was markedly decreased in PANC-1 cells transfected with HMGB1 siRNA but was significantly increased in PANC-1 cells transfected with the recombinant HMGB1 expression vector, pcDNA3.1-HMGB1 (P<0.01). The proportion of apoptotic PANC-1 cells was significantly lower in the miR-218 mimic + GEM + pcDNA3.1-HMGB1 group compared to the miR-218 mimic + GEM + HMGB1 siRNA group (P<0.01).
  
  
  CONCLUSIONS
  The expression level of miR-218 was downregulated in the GEM-resistant cell line. miR-218 promoted the sensitivity of PANC-1 cells to GEM, which was achieved mainly through regulating the expression of HMGB1 in PANC-1 cells.
authors.affiliation: 1 Department of Pancreatic Surgery, First Hospital of China Medical University, Shenyang 110001, China ; 2 Department of Otorhinolaryngology, Fengtian Hospital, Shenyang Medical University, Shenyang 110024, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 1 Department of Pancreatic Surgery, First Hospital of China Medical University, Shenyang 110001, China ; 2 Department of Otorhinolaryngology, Fengtian Hospital, Shenyang Medical University, Shenyang 110024, China.
authors.forename: Ruixia
authors.initials: R
authors.lastname: Du
authors.affiliation: 1 Department of Pancreatic Surgery, First Hospital of China Medical University, Shenyang 110001, China ; 2 Department of Otorhinolaryngology, Fengtian Hospital, Shenyang Medical University, Shenyang 110024, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Long
authors.affiliation: 1 Department of Pancreatic Surgery, First Hospital of China Medical University, Shenyang 110001, China ; 2 Department of Otorhinolaryngology, Fengtian Hospital, Shenyang Medical University, Shenyang 110024, China.
authors.forename: Kejian
authors.initials: K
authors.lastname: Guo
authors.affiliation: 1 Department of Pancreatic Surgery, First Hospital of China Medical University, Shenyang 110001, China ; 2 Department of Otorhinolaryngology, Fengtian Hospital, Shenyang Medical University, Shenyang 110024, China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Ge
authors.affiliation: 1 Department of Pancreatic Surgery, First Hospital of China Medical University, Shenyang 110001, China ; 2 Department of Otorhinolaryngology, Fengtian Hospital, Shenyang Medical University, Shenyang 110024, China.
authors.forename: Shulong
authors.initials: S
authors.lastname: Bi
authors.affiliation: 1 Department of Pancreatic Surgery, First Hospital of China Medical University, Shenyang 110001, China ; 2 Department of Otorhinolaryngology, Fengtian Hospital, Shenyang Medical University, Shenyang 110024, China.
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Xu
keywords: Pancreatic cancer; apoptosis; gemcitabine (GEM); high mobility group box 1 (HMGB1); microRNA-218 (miR-218)