Background:Transcription factor Krüppel-like factor 3(KLF3)may be involved in regulating inflammation and lymphocyte function.Immune dysfunction in sepsis involves both hyper-inflammation and immunosuppression.Ho...Background:Transcription factor Krüppel-like factor 3(KLF3)may be involved in regulating inflammation and lymphocyte function.Immune dysfunction in sepsis involves both hyper-inflammation and immunosuppression.However,studies on T-lymphocyte KLF3 expression in sepsis are lacking.Methods:We induced sepsis in mice via cecal ligation and puncture(CLP),and their survival rate over 7 days was evaluated.To identify the immune status of these mice,we assessed their cytokine levels,organ damage scores,and splenic T-lymphocyte phenotype.Finally,T-lymphocyte KLF3 expression was detected through flow cytometry.Results:Over the 7 days of observation,septic mice demonstrated 64.7%mortality.In the early stages after CLP,the proinflammatory and anti-inflammatory cytokine levels increased rapidly,multiple organ damage occurred,and splenic T lymphocytes became activated.However,the proportion of KLF3+T lymphocytes decreased.Subsequently,cytokine levels and lymphocyte activation decreased.An increase in cell apoptosis led to a substantial loss of T lymphocytes.Combined with the continual elevations in serum interleukin levels and worsening severe organ damage,septic mice may have entered a state of persistent inflammation and immunosuppression,with a simultaneous increase in KLF3 expression in T lymphocytes.Notably,KLF3 expression was negatively correlated with T-lymphocyte activation and apoptosis.Conclusions:In our septic mice,splenic T-lymphocyte KLF3 expression decreased in the early stage when the mice exhibited a systemic inflammatory response and T-lymphocyte activation.In contrast,it increased in the later stage,when persistent inflammation and immunosuppression occurred.Dynamic monitoring of KLF3 expression levels may provide aid in identifying the immune status of sepsis.展开更多
BACKGROUND Krüppel-like factor-5(KLF5)is a zinc-finger transcription factor related to tumor progression.However,the relationship between KLF5 and lung cancer remains to be identified.AIM To investigate the clini...BACKGROUND Krüppel-like factor-5(KLF5)is a zinc-finger transcription factor related to tumor progression.However,the relationship between KLF5 and lung cancer remains to be identified.AIM To investigate the clinical value of KLF5 and interference with KLF5 mRNA transcription on the effects of biological behaviors in lung squamous-cell carcinoma(LUSC).METHODS Lung KLF5 mRNA data were extracted from bioinformatics databases.Blood and tissues from a cohort of patients with benign or malignant lung diseases were collected with ethical committee consent to validate KLF5 expression via multiplex immunofluorescence and immunohistochemistry,Western blot,Enzyme Linked Immunosorbent Assay or quantitative polymerase chain reaction.Furthermore,KLF5 mRNA was silenced in lung A549 cells to validate biological behaviors in vitro and nude mouse xenograft growth in vivo,respectively.RESULTS A cohort of bioinformatics databases revealed high KLF5 mRNA expression in LUSC(P<0.001)but lower KLF5 mRNA expression in lung adenocarcinoma.Upregulated KLF5 in the lung or sera of patients with lung cancer(P<0.001)were confirmed that related to poor differentiation,lymph node or distant metastasis.Furthermore,the incidence of KLF5 levels greater than 500 ng/mL in LUSC patients was 86.7%,which was significantly greater(P<0.001)than that in cases with benign lung diseases(13.3%)or healthy controls.Functionally,silencing KLF5 mRNA with a specific shRNA significantly suppressed A549 cell proliferation,decreased cell migration,increased the ratio of G2 phase cells in vitro,and inhibited the growth of nude mouse xenografts in vivo.CONCLUSION KLF5 is a novel diagnostic biomarker or potential therapeutic target for LUSC.展开更多
Alzheimer's disease is the most prevalent chronic neurodegenerative disorder worldwide,with no sufficient cure.Ongoing research is focused on developing new therapies aimed at preventing or delaying the onset of s...Alzheimer's disease is the most prevalent chronic neurodegenerative disorder worldwide,with no sufficient cure.Ongoing research is focused on developing new therapies aimed at preventing or delaying the onset of symptoms,slowing disease progression,and improving cognitive and behavioral outcomes in individuals affected by Alzheimer's disease.Among the various pathological changes associated with this condition,blood-brain barrier(BBB)leakage plays a crucial role as it serves as a vital boundary for maintaining central nervous system(CNS)health.Preserving the integrity and functionality of the BBB is essential to protect the brain from amyloid-β accumulation,neuroinflammation,and neuronal degeneration.This review summarizes models of Alzheimer's disease characterized by BBB leakage over time.More importantly,we introduce Krüppel-l ike factor 4(KLF4),a transcription factor involved in vascular systems,and discuss its relevance to Alzheimer's disease.By elucidating the functions of KLF4 within both vascular and CNSs,this review highlights its potential role in modulating BBB integrity in Alzheimer's pathology,which may contribute to therapeutic strategies for managing this debilitating condition.展开更多
AIM:To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer. METHODS:One hundred and fifty-four patients with gastric cancer...AIM:To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer. METHODS:One hundred and fifty-four patients with gastric cancer who underwent successful curative resection were retrospectively enrolled in the study. Fifty tumor-adjacent healthy gastric tissues (≥ 5 cm from the tumor margin) obtained during the original resection were randomly selected for comparative analysis. In situ expression of KLF8 and CD34 proteins were examined by immunohistochemistry. The intratumoral microvessel density (MVD) was determined by manually counting the immunostained CD34-positive endothelial cells in three consecutive high-magnification fields (× 200). The relationship between differential KLF8 expression and MVD was assessed using Spearman's correlation coefficient test. χ2 test was performed to evaluate the effects of differential KLF8 expression on clinicopathologic factors. Kaplan-Meier and multivariate Cox survival analyses were used to assess the prognostic value of differential KLF8 expression in gastric cancer. RESULTS:Significantly higher levels of KLF8 protein were detected in gastric cancer tissues than in the adjacent non-cancerous tissues (54.5% vs 34.0%, P < 0.05). KLF8 expression was associated with tumor size (P < 0.001), local invasion (P = 0.005), regional lymph node metastasis (P = 0.029), distant metastasis (P = 0.023), and tumor node metastasis (TNM) stage (P = 0.002), as well as the MVD (r = 0.392, P < 0.001). Patients with KLF8 positive expression had poorer overall survival (P < 0.001) and cancer-specific survival (P < 0.001) than those with negative expression. Multivariate analysis demonstrated that KLF8 expression independently affected both overall and cancer-specific survival of gastric cancer patients (P = 0.035 and 0.042, respectively). CONCLUSION:KLF8 is closely associated with gastric tumor progression, angiogenesis and poor prognosis, suggesting it may represent a novel prognostic biomarker and therapeutic target for gastric cancer.展开更多
<strong>Introduction:</strong> Krüppel Like Factor 14 (KLF14) gene has recently been identified as a master gene for multiple metabolic phenotypes. The aim of the research study was to investigate the...<strong>Introduction:</strong> Krüppel Like Factor 14 (KLF14) gene has recently been identified as a master gene for multiple metabolic phenotypes. The aim of the research study was to investigate the relationship between KLF14 rs4731702 (C/T) gene polymorphism with Type 2 Diabetes Mellitus (T2DM) in a Cameroonian population. <strong>Patients and Methods:</strong> This case-control study was conducted in 85 patients with T2DM and 95 healthy normoglycemic controls. All were nonrelated, of Cameroonian origin, and were adults aged 24 years old and above. Demographic, clinical and biological data were collected, and biochemical explorations were performed using enzymatic colorimetric methods. The genotyping of KLF14 rs4731702 (CT) gene polymorphism was done by the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. Results: In comparing the Cameroonian population that consisted of 85 patients with T2DM and 95 healthy controls, the minor or risk allele of the rs4731702 (C/T) polymorphism of the KLF14 gene was T (63.53% diabetic patients vs. 26.32% healthy controls, OR = 4.877 and p < 0.0001) while the protective allele was C (36.47% diabetic patients vs. 73.68% healthy controls, OR = 0.205 and p < 0.0001). The susceptibility to T2DM was higher among subjects having the CT and TT genotypes with OR = 2.721 and p = 0.0145) and OR = 3.907 and p < 0.0001) respectively. This gene polymorphism was not preferentially associated with a specific diabetes phenotype. <strong>Conclusion:</strong> This study has demonstrated for the first time the relationship between the KLF14 rs4731702 (C/T) gene polymorphism and T2DM in this Cameroonian population. This gene polymorphism could be a promising target for personalized medicine through the development of clinical genetic testing.展开更多
Objective:To study the correlation of Krüppel-like factor 9 (KLF9) expressions in pancreatic cancer tissue with serum tumor markers and focal cell invasion.Methods: A total of 58 patients with pancreatic cancer t...Objective:To study the correlation of Krüppel-like factor 9 (KLF9) expressions in pancreatic cancer tissue with serum tumor markers and focal cell invasion.Methods: A total of 58 patients with pancreatic cancer treated in our hospital between June 2012 and May 2016 were collected, the expression of KLF9 in pancreatic cancer tissues and paracancerous tissues were measured and then patients were further divided into high KLF9 expression group and low KLF9 expression group, 29 cases in each group. Serum tumor marker levels as well as invasion gene and tumor suppressor gene expression in tumor tissue were compared between patients with different KLF9 expression.Results: KLF9 expression in pancreatic cancer tissue was significantly lower than that in paracancerous tissue;serum tumor markers CA19-9, CA242, CA50 and CEA levels of low KLF9 expression group were higher than those of high KLF9 expression group;focal invasion genes DKK-1, GSK3β and HOXB7 mRNA expression of low KLF9 expression group were higher than those of high KLF9 expression group while tumor suppressor genes Bach2, SIRT3, DPC4 and Kiss-1 mRNA expression were lower than those of high KLF9 expression group.Conclusion: The expression of KLF9 decreases in pancreatic cancer tissues, and the expression of KLF9 is negatively correlated with the malignant degree of tumor.展开更多
Background Pancreatic cancer is a lethal disease that is often diagnosed at an advanced stage.There is a lack of information to predict the prognosis of pancreatic cancer.Krüppel-like factor （KLF） 8 has been fo...Background Pancreatic cancer is a lethal disease that is often diagnosed at an advanced stage.There is a lack of information to predict the prognosis of pancreatic cancer.Krüppel-like factor （KLF） 8 has been found to be deregulated in multiple cancers,and its high expression was correlated with poor prognosis.However,so far,no information was reported about the expression of KLF8 in pancreatic cancer.In the present study,we investigated,possibly for the first time,the expression of KLF8 in pancreatic cancer samples and analyzed its correlation with clinical parameters and overall survival （OS） rate.Methods We used immunohistochemical staining to detect KLF8 in 68 samples from patients who underwent surgery and its correlation with the clinicopathological characteristics.We used Kaplan-Meier curve to analyze the relationship between KLF8 expression and the OS time.Univariate analysis was performed in addition to multivariate hazard models with clinicopathological features to assess KLF8 as an independent prognostic factor.Results KLF8 was present in the cytoplasm of pancreatic cancer cells and 52.9％ of the 68 cases had positive expression.KLF8 expression was not associated with sex,age,tumor location,lymph node stage,and metastasis stage,but was associated with tumor stage （P=0.04）.Kaplan-Meier method demonstrated that patients with negative expression of KLF8 had a better prognosis.In univariate and multivariate models,KLF8 was a significant predictor of OS in pancreatic cancer.Conclusion Our results revealed that KLF8 may be a potential prognostic factor for pancreatic cancer.展开更多
Vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krüppel-like factor 5 (KLF5) has been i...Vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krüppel-like factor 5 (KLF5) has been identified as a significant factor in cardiovascular diseases during the last two decades. This review provides a mechanism network of function and regulation of KLF5 in vascular remodeling based on newly published data and gives a summary of its potential therapeutic applications. KLF5 modulates numerous biological processes, which play essential parts in the development of vascular remodeling, such as cell proliferation, phenotype switch, extracellular matrix deposition, inflammation, and angiogenesis by altering downstream genes and signaling pathways. Considering its essential functions, KLF5 could be developed as a potent therapeutic target in vascular disorders.展开更多
Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasi...Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss accelerates development and progression of cancer. The present study examined the relationship between KLF4 and markers of EMT in CRC. Methods: Immunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer. Results: We found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections, we observed a negative correlation between KLF4 levels and mesenchymal markers including TWIST, β-catenin, claudin-1, N-cadherin, and ;vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice, KLF4 levels were negatively correlated with mesenchymal markers including SNAI2, β-catenin, and vimentin and positively correlated with the epithelial marker E-cadherin. Conclusion: These findings suggest that the loss of KLF4 expression is a potentially significant indicator of EMT in CRC.展开更多
Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health.However, to date, no approved therapeutic drugs have been developed. Dietary interventions with naturalproducts ...Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health.However, to date, no approved therapeutic drugs have been developed. Dietary interventions with naturalproducts have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompoundwith antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN canameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying thesebeneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipidaccumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis(NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line andthe liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type andthe regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophageM2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovereda new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFNmight be protective against NASH.展开更多
Krüppel-like factor(KLF) family proteins are transcription factors that regulate numerous cellular functions, such as cell proliferation, differentiation, and cell death. Posttranslational modification of KLF pro...Krüppel-like factor(KLF) family proteins are transcription factors that regulate numerous cellular functions, such as cell proliferation, differentiation, and cell death. Posttranslational modification of KLF proteins is important for their transcriptional activities and biological functions. One KLF family member with important roles in cell proliferation and tumorigenesis is KLF5. The function of KLF5 is tightly controlled by post-translational modifications, including SUMOylation, phosphorylation, and ubiquitination. Recent studies from our lab and others' have demonstrated that the tumor suppressor FBW7 is an essential E3 ubiquitin ligase that targets KLF5 for ubiquitination and degradation. KLF5 contains functional Cdc4 phospho-degrons(CPDs), which are required for its interaction with FBW7. Mutation of CPDs in KLF5 blocks the ubiquitination and degradation of KLF5 by FBW7. The protein kinase Glycogen synthase kinase 3β is involved in the phosphorylation of KLF5 CPDs. In both cancer cell lines and mousemodels, it has been shown that FBW7 regulates the expression of KLF5 target genes through the modulation of KLF5 stability. In this review, we summarize the current progress on delineating FBW7-mediated KLF5 ubiquitination and degradation.展开更多
Salidroside is extensively used as a herbal medicine worldwide, and it has been shown to protect against disruption of endothelial homeostasis and act as an anti-aging agent. The present study aimed to investigate the...Salidroside is extensively used as a herbal medicine worldwide, and it has been shown to protect against disruption of endothelial homeostasis and act as an anti-aging agent. The present study aimed to investigate the ameliorative effects of salidroside on homocysteine (Hcy)-induced cell senescence in human umbilical vein endothelial cells (HUVECs) that were mediated via inhibition of Krüppel-like factor 4 (KLF4). An endothelial cell senescence model was induced by Hcy. The cell viability, activities of telomerase and lactate dehydrogenase (LDH), and the level of reactive oxygen species were determined using commercial kits. The expression levels of KLF4, p53 and p21 were determined via western blot analysis, whereas the mRNA expression levels of KLF4 were detected by reverse transcription-quantitative PCR. Small interfering RNA-mediated knockdown of KLF4 was found to reverse Hcy-induced cell senescence. Hcy treatment led to an accelerated cell senescence, as evidenced by decreases in both cell viability and telomerase activity, whereas increases were noted in the leakage of LDH and the level of reactive oxygen species, in addition to an up-regulation of the protein levels of p53 and p21, and up-regulation of KLF4 at both the mRNA and protein level. Treatment with salidroside ameliorated Hcy-induced cell senescence in a dose-dependent manner. Taken together, these results suggested that Hcy may induce cell senescence through upregulation of KLF4, and this may be reversed by treatment with salidroside. Therefore, salidroside was shown to inhibit Hcy-induced cell senescence through KLF4 inhibition.展开更多
Kruppel-like factors(KLFs) are a subclass of the zinc finger family of DNA-binding transcription factors. The nomenclature is based on the homology to the DNA-binding domain of the drosophila protein kruppel.To date,1...Kruppel-like factors(KLFs) are a subclass of the zinc finger family of DNA-binding transcription factors. The nomenclature is based on the homology to the DNA-binding domain of the drosophila protein kruppel.To date,17 members of KLF family have been identified in mammalian cells.KLF family is implicated in many bio-展开更多
基金supported by grants from theNational Key Specialty Construction Project of China[grant number 2023-141]the National High Level Hospital Clinical Research Funding(Scientific Research Feed Fund of Peking University First Hospital)[grant number 2022SF23].
文摘Background:Transcription factor Krüppel-like factor 3(KLF3)may be involved in regulating inflammation and lymphocyte function.Immune dysfunction in sepsis involves both hyper-inflammation and immunosuppression.However,studies on T-lymphocyte KLF3 expression in sepsis are lacking.Methods:We induced sepsis in mice via cecal ligation and puncture(CLP),and their survival rate over 7 days was evaluated.To identify the immune status of these mice,we assessed their cytokine levels,organ damage scores,and splenic T-lymphocyte phenotype.Finally,T-lymphocyte KLF3 expression was detected through flow cytometry.Results:Over the 7 days of observation,septic mice demonstrated 64.7%mortality.In the early stages after CLP,the proinflammatory and anti-inflammatory cytokine levels increased rapidly,multiple organ damage occurred,and splenic T lymphocytes became activated.However,the proportion of KLF3+T lymphocytes decreased.Subsequently,cytokine levels and lymphocyte activation decreased.An increase in cell apoptosis led to a substantial loss of T lymphocytes.Combined with the continual elevations in serum interleukin levels and worsening severe organ damage,septic mice may have entered a state of persistent inflammation and immunosuppression,with a simultaneous increase in KLF3 expression in T lymphocytes.Notably,KLF3 expression was negatively correlated with T-lymphocyte activation and apoptosis.Conclusions:In our septic mice,splenic T-lymphocyte KLF3 expression decreased in the early stage when the mice exhibited a systemic inflammatory response and T-lymphocyte activation.In contrast,it increased in the later stage,when persistent inflammation and immunosuppression occurred.Dynamic monitoring of KLF3 expression levels may provide aid in identifying the immune status of sepsis.
基金Supported by Jiangsu Commission of Health of China,No.M2020096.
文摘BACKGROUND Krüppel-like factor-5(KLF5)is a zinc-finger transcription factor related to tumor progression.However,the relationship between KLF5 and lung cancer remains to be identified.AIM To investigate the clinical value of KLF5 and interference with KLF5 mRNA transcription on the effects of biological behaviors in lung squamous-cell carcinoma(LUSC).METHODS Lung KLF5 mRNA data were extracted from bioinformatics databases.Blood and tissues from a cohort of patients with benign or malignant lung diseases were collected with ethical committee consent to validate KLF5 expression via multiplex immunofluorescence and immunohistochemistry,Western blot,Enzyme Linked Immunosorbent Assay or quantitative polymerase chain reaction.Furthermore,KLF5 mRNA was silenced in lung A549 cells to validate biological behaviors in vitro and nude mouse xenograft growth in vivo,respectively.RESULTS A cohort of bioinformatics databases revealed high KLF5 mRNA expression in LUSC(P<0.001)but lower KLF5 mRNA expression in lung adenocarcinoma.Upregulated KLF5 in the lung or sera of patients with lung cancer(P<0.001)were confirmed that related to poor differentiation,lymph node or distant metastasis.Furthermore,the incidence of KLF5 levels greater than 500 ng/mL in LUSC patients was 86.7%,which was significantly greater(P<0.001)than that in cases with benign lung diseases(13.3%)or healthy controls.Functionally,silencing KLF5 mRNA with a specific shRNA significantly suppressed A549 cell proliferation,decreased cell migration,increased the ratio of G2 phase cells in vitro,and inhibited the growth of nude mouse xenografts in vivo.CONCLUSION KLF5 is a novel diagnostic biomarker or potential therapeutic target for LUSC.
基金Guangzhou Municipal Science and Technology Project,Grant/Award Number:2024A03J0071National Natural Science Foundation of China,Grant/Award Number:82471386Key Laboratory of Guangdong Higher Education Institutes,Grant/Award Number:2021KSYS009。
文摘Alzheimer's disease is the most prevalent chronic neurodegenerative disorder worldwide,with no sufficient cure.Ongoing research is focused on developing new therapies aimed at preventing or delaying the onset of symptoms,slowing disease progression,and improving cognitive and behavioral outcomes in individuals affected by Alzheimer's disease.Among the various pathological changes associated with this condition,blood-brain barrier(BBB)leakage plays a crucial role as it serves as a vital boundary for maintaining central nervous system(CNS)health.Preserving the integrity and functionality of the BBB is essential to protect the brain from amyloid-β accumulation,neuroinflammation,and neuronal degeneration.This review summarizes models of Alzheimer's disease characterized by BBB leakage over time.More importantly,we introduce Krüppel-l ike factor 4(KLF4),a transcription factor involved in vascular systems,and discuss its relevance to Alzheimer's disease.By elucidating the functions of KLF4 within both vascular and CNSs,this review highlights its potential role in modulating BBB integrity in Alzheimer's pathology,which may contribute to therapeutic strategies for managing this debilitating condition.
基金Supported by The Shandong Province Natural Science Foundation of China, No. ZR2010HZ004the National Key Clinical Medical Specialties Foundation
文摘AIM:To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer. METHODS:One hundred and fifty-four patients with gastric cancer who underwent successful curative resection were retrospectively enrolled in the study. Fifty tumor-adjacent healthy gastric tissues (≥ 5 cm from the tumor margin) obtained during the original resection were randomly selected for comparative analysis. In situ expression of KLF8 and CD34 proteins were examined by immunohistochemistry. The intratumoral microvessel density (MVD) was determined by manually counting the immunostained CD34-positive endothelial cells in three consecutive high-magnification fields (× 200). The relationship between differential KLF8 expression and MVD was assessed using Spearman's correlation coefficient test. χ2 test was performed to evaluate the effects of differential KLF8 expression on clinicopathologic factors. Kaplan-Meier and multivariate Cox survival analyses were used to assess the prognostic value of differential KLF8 expression in gastric cancer. RESULTS:Significantly higher levels of KLF8 protein were detected in gastric cancer tissues than in the adjacent non-cancerous tissues (54.5% vs 34.0%, P < 0.05). KLF8 expression was associated with tumor size (P < 0.001), local invasion (P = 0.005), regional lymph node metastasis (P = 0.029), distant metastasis (P = 0.023), and tumor node metastasis (TNM) stage (P = 0.002), as well as the MVD (r = 0.392, P < 0.001). Patients with KLF8 positive expression had poorer overall survival (P < 0.001) and cancer-specific survival (P < 0.001) than those with negative expression. Multivariate analysis demonstrated that KLF8 expression independently affected both overall and cancer-specific survival of gastric cancer patients (P = 0.035 and 0.042, respectively). CONCLUSION:KLF8 is closely associated with gastric tumor progression, angiogenesis and poor prognosis, suggesting it may represent a novel prognostic biomarker and therapeutic target for gastric cancer.
文摘<strong>Introduction:</strong> Krüppel Like Factor 14 (KLF14) gene has recently been identified as a master gene for multiple metabolic phenotypes. The aim of the research study was to investigate the relationship between KLF14 rs4731702 (C/T) gene polymorphism with Type 2 Diabetes Mellitus (T2DM) in a Cameroonian population. <strong>Patients and Methods:</strong> This case-control study was conducted in 85 patients with T2DM and 95 healthy normoglycemic controls. All were nonrelated, of Cameroonian origin, and were adults aged 24 years old and above. Demographic, clinical and biological data were collected, and biochemical explorations were performed using enzymatic colorimetric methods. The genotyping of KLF14 rs4731702 (CT) gene polymorphism was done by the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. Results: In comparing the Cameroonian population that consisted of 85 patients with T2DM and 95 healthy controls, the minor or risk allele of the rs4731702 (C/T) polymorphism of the KLF14 gene was T (63.53% diabetic patients vs. 26.32% healthy controls, OR = 4.877 and p < 0.0001) while the protective allele was C (36.47% diabetic patients vs. 73.68% healthy controls, OR = 0.205 and p < 0.0001). The susceptibility to T2DM was higher among subjects having the CT and TT genotypes with OR = 2.721 and p = 0.0145) and OR = 3.907 and p < 0.0001) respectively. This gene polymorphism was not preferentially associated with a specific diabetes phenotype. <strong>Conclusion:</strong> This study has demonstrated for the first time the relationship between the KLF14 rs4731702 (C/T) gene polymorphism and T2DM in this Cameroonian population. This gene polymorphism could be a promising target for personalized medicine through the development of clinical genetic testing.
文摘Objective:To study the correlation of Krüppel-like factor 9 (KLF9) expressions in pancreatic cancer tissue with serum tumor markers and focal cell invasion.Methods: A total of 58 patients with pancreatic cancer treated in our hospital between June 2012 and May 2016 were collected, the expression of KLF9 in pancreatic cancer tissues and paracancerous tissues were measured and then patients were further divided into high KLF9 expression group and low KLF9 expression group, 29 cases in each group. Serum tumor marker levels as well as invasion gene and tumor suppressor gene expression in tumor tissue were compared between patients with different KLF9 expression.Results: KLF9 expression in pancreatic cancer tissue was significantly lower than that in paracancerous tissue;serum tumor markers CA19-9, CA242, CA50 and CEA levels of low KLF9 expression group were higher than those of high KLF9 expression group;focal invasion genes DKK-1, GSK3β and HOXB7 mRNA expression of low KLF9 expression group were higher than those of high KLF9 expression group while tumor suppressor genes Bach2, SIRT3, DPC4 and Kiss-1 mRNA expression were lower than those of high KLF9 expression group.Conclusion: The expression of KLF9 decreases in pancreatic cancer tissues, and the expression of KLF9 is negatively correlated with the malignant degree of tumor.
基金This study was supported by the National Natural Science Foundation of China，China Health Industry Research and Special Fund
文摘Background Pancreatic cancer is a lethal disease that is often diagnosed at an advanced stage.There is a lack of information to predict the prognosis of pancreatic cancer.Krüppel-like factor （KLF） 8 has been found to be deregulated in multiple cancers,and its high expression was correlated with poor prognosis.However,so far,no information was reported about the expression of KLF8 in pancreatic cancer.In the present study,we investigated,possibly for the first time,the expression of KLF8 in pancreatic cancer samples and analyzed its correlation with clinical parameters and overall survival （OS） rate.Methods We used immunohistochemical staining to detect KLF8 in 68 samples from patients who underwent surgery and its correlation with the clinicopathological characteristics.We used Kaplan-Meier curve to analyze the relationship between KLF8 expression and the OS time.Univariate analysis was performed in addition to multivariate hazard models with clinicopathological features to assess KLF8 as an independent prognostic factor.Results KLF8 was present in the cytoplasm of pancreatic cancer cells and 52.9％ of the 68 cases had positive expression.KLF8 expression was not associated with sex,age,tumor location,lymph node stage,and metastasis stage,but was associated with tumor stage （P=0.04）.Kaplan-Meier method demonstrated that patients with negative expression of KLF8 had a better prognosis.In univariate and multivariate models,KLF8 was a significant predictor of OS in pancreatic cancer.Conclusion Our results revealed that KLF8 may be a potential prognostic factor for pancreatic cancer.
基金The work was supported by the National Natural Science Foundation of China(81970360).
文摘Vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krüppel-like factor 5 (KLF5) has been identified as a significant factor in cardiovascular diseases during the last two decades. This review provides a mechanism network of function and regulation of KLF5 in vascular remodeling based on newly published data and gives a summary of its potential therapeutic applications. KLF5 modulates numerous biological processes, which play essential parts in the development of vascular remodeling, such as cell proliferation, phenotype switch, extracellular matrix deposition, inflammation, and angiogenesis by altering downstream genes and signaling pathways. Considering its essential functions, KLF5 could be developed as a potent therapeutic target in vascular disorders.
基金grants from the National Institutes of Health awarded to Yang VW (CA084197)
文摘Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss accelerates development and progression of cancer. The present study examined the relationship between KLF4 and markers of EMT in CRC. Methods: Immunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer. Results: We found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections, we observed a negative correlation between KLF4 levels and mesenchymal markers including TWIST, β-catenin, claudin-1, N-cadherin, and ;vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice, KLF4 levels were negatively correlated with mesenchymal markers including SNAI2, β-catenin, and vimentin and positively correlated with the epithelial marker E-cadherin. Conclusion: These findings suggest that the loss of KLF4 expression is a potentially significant indicator of EMT in CRC.
基金supported by the Science and Technology project of Henan Province(202102310142)the National Natural Science Foundation of China(32001806)。
文摘Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health.However, to date, no approved therapeutic drugs have been developed. Dietary interventions with naturalproducts have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompoundwith antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN canameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying thesebeneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipidaccumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis(NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line andthe liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type andthe regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophageM2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovereda new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFNmight be protective against NASH.
基金Supported by Grants from National Basic Research Program of China,973 program,No.2010CB529704 and No.2012CB910404National Natural Science Foundation of China,No.30800587,No.30971521,and No.31171338+1 种基金the Science and Technology Commission of Shanghai Municipality,No.11DZ2260300a scholar of the Shanghai Rising-Star Program from Science and Technology Commission of Shanghai Municipality,No.09QA1401900 to Wang P
文摘Krüppel-like factor(KLF) family proteins are transcription factors that regulate numerous cellular functions, such as cell proliferation, differentiation, and cell death. Posttranslational modification of KLF proteins is important for their transcriptional activities and biological functions. One KLF family member with important roles in cell proliferation and tumorigenesis is KLF5. The function of KLF5 is tightly controlled by post-translational modifications, including SUMOylation, phosphorylation, and ubiquitination. Recent studies from our lab and others' have demonstrated that the tumor suppressor FBW7 is an essential E3 ubiquitin ligase that targets KLF5 for ubiquitination and degradation. KLF5 contains functional Cdc4 phospho-degrons(CPDs), which are required for its interaction with FBW7. Mutation of CPDs in KLF5 blocks the ubiquitination and degradation of KLF5 by FBW7. The protein kinase Glycogen synthase kinase 3β is involved in the phosphorylation of KLF5 CPDs. In both cancer cell lines and mousemodels, it has been shown that FBW7 regulates the expression of KLF5 target genes through the modulation of KLF5 stability. In this review, we summarize the current progress on delineating FBW7-mediated KLF5 ubiquitination and degradation.
文摘Salidroside is extensively used as a herbal medicine worldwide, and it has been shown to protect against disruption of endothelial homeostasis and act as an anti-aging agent. The present study aimed to investigate the ameliorative effects of salidroside on homocysteine (Hcy)-induced cell senescence in human umbilical vein endothelial cells (HUVECs) that were mediated via inhibition of Krüppel-like factor 4 (KLF4). An endothelial cell senescence model was induced by Hcy. The cell viability, activities of telomerase and lactate dehydrogenase (LDH), and the level of reactive oxygen species were determined using commercial kits. The expression levels of KLF4, p53 and p21 were determined via western blot analysis, whereas the mRNA expression levels of KLF4 were detected by reverse transcription-quantitative PCR. Small interfering RNA-mediated knockdown of KLF4 was found to reverse Hcy-induced cell senescence. Hcy treatment led to an accelerated cell senescence, as evidenced by decreases in both cell viability and telomerase activity, whereas increases were noted in the leakage of LDH and the level of reactive oxygen species, in addition to an up-regulation of the protein levels of p53 and p21, and up-regulation of KLF4 at both the mRNA and protein level. Treatment with salidroside ameliorated Hcy-induced cell senescence in a dose-dependent manner. Taken together, these results suggested that Hcy may induce cell senescence through upregulation of KLF4, and this may be reversed by treatment with salidroside. Therefore, salidroside was shown to inhibit Hcy-induced cell senescence through KLF4 inhibition.
文摘Kruppel-like factors(KLFs) are a subclass of the zinc finger family of DNA-binding transcription factors. The nomenclature is based on the homology to the DNA-binding domain of the drosophila protein kruppel.To date,17 members of KLF family have been identified in mammalian cells.KLF family is implicated in many bio-
