Zhe Liu1, Ruixia Du1, Jin Long1, Kejian Guo1, Chunlin Ge1, Shulong Bi1, Yuanhong Xu1. 1. 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.
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.
OBJECTIVE: The purpose of this study was to examine the effect of gemcitabine (GEM) on microRNA-218 (miR-218) expression in humanpancreatic 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.
Entities:
Keywords:
Pancreatic cancer; apoptosis; gemcitabine (GEM); high mobility group box 1 (HMGB1); microRNA-218 (miR-218)
Authors: André M Leite-Moreira; André P Lourenço; Inês Falcão-Pires; Adelino F Leite-Moreira Journal: Drug Discov Today Date: 2013-08-13 Impact factor: 7.851
Authors: C S Fuchs; S Azevedo; T Okusaka; J-L Van Laethem; L R Lipton; H Riess; C Szczylik; M J Moore; M Peeters; G Bodoky; M Ikeda; B Melichar; R Nemecek; S Ohkawa; A Świeboda-Sadlej; S A Tjulandin; E Van Cutsem; R Loberg; V Haddad; J L Gansert; B A Bach; A Carrato Journal: Ann Oncol Date: 2015-01-21 Impact factor: 32.976
Authors: Jaehoon Lee; Hee Seung Lee; Soo Been Park; Chanyang Kim; Kahee Kim; Dawoon E Jung; Si Young Song Journal: Int J Mol Sci Date: 2021-01-20 Impact factor: 5.923