KLF5 suppresses TRAIL-induced cell apoptosis in PC-3 prostate cancer cells / 西安交通大学学报(医学版)

Objective: To explore the possibility of promoting tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis in prostate cancer PC-3 cell by inhibiting Krüppel-like factor 5 (KLF5). Methods: MTT assay, flow cytometry, Western blot assay and qRT-PCR assay were deployed to detect the cell viability, apoptosis and apoptotic markers in KLF5-inhibited and TRAIL-induced PC-3 cells. Results: After KLF5 was inhibited in TRAIL-induced PC-3 cells, cell viability reduced, apoptosis enhanced, the expressions of DR4 and DR5 increased while the expression of cellular fas-associated death domain-like interleukin-1β converting enzyme inhibitory protein (c-FLIP) decreased. Conclusion: Inhibiting KLF5 suppresses cell viability by promoting TRAIL-induced apoptosis in prostate cancer cell PC-3. It may be a potential means to treat hormone-insensitive prostate cancer.

The Krüppel-like factor (KLF5) as a predictive biomarker in preoperative chemoradiation therapy for rectal cancer

PURPOSE: Preoperative chemoradiation therapy (CRT) has become the standard treatment for patients with locally advanced rectal cancer, 15%–30% of patients still progress while being treated with CRT. The aim of this study was to identify as important biomarker of poor response and evaluate the mechanism associated with CRT resistance. METHODS: This study included 60 human colon tumour pre-irradiation specimens. Expressions of epidermal growth factor receptor (EGFR), p53, Krüppel-like factor 5 (KLF5), C-ern, Ki67 were assessed and correlated with tumor regression grades and complete remission. We added in vitro study with biomarker which has been identified as important biomarker of poor response to evaluate the mechanism associated with CRT resistance. RESULTS: Pathologic complete remission (pCR) was achieved by 9 patients (18%). EGFR and KLF5 were significantly associated with pCR (P = 0.048, P = 0.023, respectfully). And multivariate analysis showed high KLF5 intensity was worse factor for pCR (P = 0.012). In vitro study, radiation or chemotherapy therapy stabilized KLF5 protein levels in a time- and dose-depended manner in HCT116 and Caco-2 cells. KLF5 overexpression in HCT116 stable cell line showed significantly better cell viability by increasing cyclinD1 and b-catenin compared to control cells in MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, suggesting that KLF5 mediates cell survival. CONCLUSION: KLF5 was significantly associated with the presence of KRAS mutations, and KLF5 was an independent poor response predictor of CRT in rectal cancer. Our study is pilot study and more research will be needed in the future.

Mifepristone derivative FZU-00,033 suppresses triple-negative breast cancer cell viability via down-regula-ting KLF5 expression / 医学研究生学报

Objective Mifepristone (MIF) can inhibit triple-negative breast cancer cell (TNBC) survival at high concentra-tions. The purpose of the present study is to study the effect of mifepristone derivatives on triple-negative breast cancer cell (TNBC) survival at low concentrations. Methods SUM149PT and HCC1937 triple negative breast cancer cells were used in the study; the experiment was set in four groups: DMSO group,MIF group(10 μmol/L MIF),5 μmol/L FZU-00,033 group and 10 μmol/L FZU-00,033 group. They were treated with 24,48,72 h,and cell viability was measured by SRB. KLF5 overexpression HCC1937 cell line was used in the study; the experiment was set in four groups: PCDH-DMSO group(PCDH vector,DMSO),PCDH-FZU-00,033 group (PCDH vector,10 μmol/L FZU-00,033),KLF5-DMSO group(overexpress KLF5,DMSO),KLF5-FZU-00,033 group(overexpress KLF5,10 μmol/L FZU-00,033). Cell apoptosis was investigated by detecting PARP cleavage using Western blot. In order to investi-gate how FZU-00,033 reduced cell viability,we detected KLF5 protein expression after drug treatment. On the basic of the original PC-DH-DMSO group,PCDH-FZU-00,033 group,KLF5-DMSO group and KLF5-FZU-00,033 group,5 μmol/L PCDH-FZU-00,033 group (PCDH vector,5 μmol/L FZU-00,033),5 μmol/L KLF5-FZU-00,033 group(overexpress KLF5,5 μmol/L FZU-00,033). Western blot was used to detect the effect of FZU-00,033 in KLF5 overexpression cell line. Results Compared with DMSO group,5 μmol/L FZU-00,033 group,10 μmol/L FZU-00,033 group and MIF group decreasd TNBC cell viability more efficiently at 24,48,72h (P<0.01); the cell survival rate of DMSO group,5 μmol/L FZU-00,033 group,10 μmol/L FZU-00,033 group and MIF group was [(100±4)%,(17±2)%,(5±1)%,(58±1)%] respectively in SUM149PT cell line and was [(100±7)%,(39±1)%,(30±1)%,(62±1)%] respectively in HCC1937 cell line. Compared with MIF group,5 μmol/L FZU-00,033 group and 10 μmol/L FZU-00,033 group decreasd TNBC cell viability more efficiently at 24,48,72 h (P<0.01). Compared with DMSO group,5 μmol/L FZU-00,033 group,10 μmol/L FZU-00,033 group and MIF group suppressed KLF5 expression more potently and increased cell apoptosis. Com-pared with 10 μmol/L MIF group,5 μmol/L FZU-00,033 group and 10 μmol/L FZU-00,033 group significantly increased apoptosis. Compared with PCDH-DMSO group,10 μmol/L PCDH-FZU-00,033 group decreasd TNBC cell viability more efficiently at 48,72 h and cell survial rate was [(100±6)% vs (39±2)%,P<0.05] and [(100±3)% vs (21±1)%,P<0.05] respectively. Compared with KLF5-DMSO group,10 μmol/L KLF5-FZU-00,033 group decreasd TNBC cell viability more efficiently at 48,72h and cell survial rate was [(100±1)% vs (47±1)%,P<0.05] and [(100±1)% vs (27±1)%,P<0.05] respectively; Meanwhile,Compared with 10 μmol/L PCDH-FZU-00,033 group,10 μmol/L KLF5-FZU-00,033 group increased TNBC cell viability more efficiently at 48,72 h (P<0.05). Compared with PCDH-DMSO group,5 μmol/L PCDH-FZU-00,033 group and 10 μmol/L PCDH-FZU-00,033 group in-creased cell apoptosis; Compared with KLF5-DMSO group,5 μmol/L KLF5-FZU-00,033 group and 10 μmol/L KLF5-FZU-00,033 group increased cell apoptosis. Conclusion Novel mifepristone derivative FZU-00,033 suppressed TNBC cell viability partially through suppressing KLF5 expression.

Evaluation of TAZ and KLF5 expression and their clinical significance in hepato-cellular carcinoma / 中国免疫学杂志

Objective:To investigate the expression of TAZ and KLF5 and their clinical significance in hepatocellular carcinoma ( HCC).Methods:We freshly collected 76 samples of surgically resected HCC and matched normal tumor-adjacent tissues and detected TAZ and KLF5 expression in these samples using immunohistochemical staining.The clinical significance of TAZ and KLF5 protein expression were analysed.Results:The protein expression of TAZ and KLF5 in HCC tissues was significantly higher than those in matched normal tumor-adjacent tissues ( P=0.001;P=0.035 ).Clinicopathological analysis suggested that TAZ and KLF5 protein expression were associated with histopathological differentiation ( P=0.007;P=0.047 ) and TNM stage ( P=0.009;P=0.040).TAZ was positively correlated with KLF5 protein in HCC tissues (r=0.651,P=0.003).Conclusion:The high-expression of TAZ and KLF5 are correlated with poor clinicopathological characteristics,and TAZ is positively associated with KLF5 in HCC tissues, suggesting that TAZ may promote tumor progression through inhibition of KLF5 protein degradation in HCC.

TT Mutant Homozygote of Kruppel-like Factor 5 Is a Key Factor for Increasing Basal Metabolic Rate and Resting Metabolic Rate in Korean Elementary School Children

We investigated the contribution of genetic variations of KLF5 to basal metabolic rate (BMR) and resting metabolic rate (RMR) and the inhibition of obesity in Korean children. A variation of KLF5 (rs3782933) was genotyped in 62 Korean children. Using multiple linear regression analysis, we developed a model to predict BMR in children. We divided them into several groups; normal versus overweight by body mass index (BMI) and low BMR versus high BMR by BMR. There were no differences in the distributions of alleles and genotypes between each group. The genetic variation of KLF5 gene showed a significant correlation with several clinical factors, such as BMR, muscle, low-density lipoprotein cholesterol, and insulin. Children with the TT had significantly higher BMR than those with CC (p = 0.030). The highest muscle was observed in the children with TT compared with CC (p = 0.032). The insulin and C-peptide values were higher in children with TT than those with CC (p= 0.029 vs. p = 0.004, respectively). In linear regression analysis, BMI and muscle mass were correlated with BMR, whereas insulin and C-peptide were not associated with BMR. In the high-BMR group, we observed that higher muscle, fat mass, and C-peptide affect the increase of BMR in children with TT (p < 0.001, p < 0.001, and p = 0.018, respectively), while Rohrer's index could explain the usual decrease in BMR (adjust r2 = 1.000, p < 0.001, respectively). We identified a novel association between TT of KLF5 rs3782933 and BMR in Korean children. We could make better use of the variation within KLF5 in a future clinical intervention study of obesity.