Metastasis is crucial for the mortality of non-small cell lung carcinoma(NSCLC) patients.The epithelial-mesenchymal transition(EMT) plays a critical role in regulating tumor metastasis.Glioma-associated oncogene 1(Gli...Metastasis is crucial for the mortality of non-small cell lung carcinoma(NSCLC) patients.The epithelial-mesenchymal transition(EMT) plays a critical role in regulating tumor metastasis.Glioma-associated oncogene 1(Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein,we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.展开更多
Background Studies have shown that abnormal activation of the sonic hedgehog pathway is closely related to tumorigenesis in central nervous system. This study aimed to investigate the role of the sonic hedgehog signal...Background Studies have shown that abnormal activation of the sonic hedgehog pathway is closely related to tumorigenesis in central nervous system. This study aimed to investigate the role of the sonic hedgehog signaling pathway in the occurrence of brainstem and supratentorial glioma. Methods Real-time quantitative reverse transcription polymerase chain reaction （qRT-PCR） and immunohistochemistry were used to detect the expression of sonic hedgehog-related components in 5 specimens of normal brain tissue, 10 of grade II brainstem glioma, and 10 of grade II supratentorial glioma. The significance of differences between two groups was determined using the Mann-Whitney U test or the two-sample test according to the results of normality distribution tests. Results The mRNA expression levels of sonic hedgehog-related genes were higher in brainstem astrocytomas than in supratentorial astrocytomas and normal brain tissue. The level of protein patched homolog 1 （PTCH1） was significantly higher in brainstem astrocytomas than in supratentorial astrocytomas and normal brain tissue （P 〈0.01）. Immunohistochemistry semi-quantitative analysis was consistent with the qRT-PCR result that PTCH1 expression was increased significantly in brainstem astrocytomas at the protein level （P 〈0.05）. Conclusions Enhanced PTCH1 expression and activation of the sonic hedgehog pathway are involved in brainstem glioma. This may be related to the difference in malignant biological behavior between brainstem and hemispheric glioma and could be an ideal therapeutic target in brainstem glioma.展开更多
Non-alcoholic fatty liver disease(NAFLD)is a common chronic disease characterized by excessive fat accumulation in hepatocytes in the absence of alcohol consumption.Modern trends towards excessive calorie intake and s...Non-alcoholic fatty liver disease(NAFLD)is a common chronic disease characterized by excessive fat accumulation in hepatocytes in the absence of alcohol consumption.Modern trends towards excessive calorie intake and sedentary life styles have increased the prevalence of NAFLD accompanied by obesity and type 2 diabetes.However,the molecular mechanisms underlying the initiation and progression of NAFLD are not clear.Zinc finger proteins(ZFPs)are a superfamily of metalloproteins that contain zinc finger motifs.ZFPs play diverse physiological roles in tissue homeostasis and also contribute to many pathological conditions,including metabolic,cardiovascular,and neurodegenerative diseases and various types of cancer.In this review,we highlight our current knowledge of several ZFPs that play critical roles in the progression of NAFLD,describe their mechanistic functional networks,and discuss the potential for ZFPs as therapeutic targets for NAFLD.展开更多
基金supported by National Natural Science Foundation of China(82104201)the GuangDong Basic and Applied Basic Research Foundation(2019A1515110058,China)+2 种基金the Science and Technology Program of Guangzhou(202002030026,China)the open research funds from the Sixth Affiliated Hospital of Guangzhou Medical University,Qingyuan People’s Hospital(202011-306,China)to Xueping Lei,National Natural Science Foundation of China(81903607)to Songpei Li,Research Program of Guangzhou Education Bureau(202032845,China)the Science and Technology Program of Guangzhou(202102020017,China)to Qiudi Deng.
文摘Metastasis is crucial for the mortality of non-small cell lung carcinoma(NSCLC) patients.The epithelial-mesenchymal transition(EMT) plays a critical role in regulating tumor metastasis.Glioma-associated oncogene 1(Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein,we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.
基金This work was supported by grants-from the National Natural Science Foundation of China （No. 30772237 and No. 30900479）.
文摘Background Studies have shown that abnormal activation of the sonic hedgehog pathway is closely related to tumorigenesis in central nervous system. This study aimed to investigate the role of the sonic hedgehog signaling pathway in the occurrence of brainstem and supratentorial glioma. Methods Real-time quantitative reverse transcription polymerase chain reaction （qRT-PCR） and immunohistochemistry were used to detect the expression of sonic hedgehog-related components in 5 specimens of normal brain tissue, 10 of grade II brainstem glioma, and 10 of grade II supratentorial glioma. The significance of differences between two groups was determined using the Mann-Whitney U test or the two-sample test according to the results of normality distribution tests. Results The mRNA expression levels of sonic hedgehog-related genes were higher in brainstem astrocytomas than in supratentorial astrocytomas and normal brain tissue. The level of protein patched homolog 1 （PTCH1） was significantly higher in brainstem astrocytomas than in supratentorial astrocytomas and normal brain tissue （P 〈0.01）. Immunohistochemistry semi-quantitative analysis was consistent with the qRT-PCR result that PTCH1 expression was increased significantly in brainstem astrocytomas at the protein level （P 〈0.05）. Conclusions Enhanced PTCH1 expression and activation of the sonic hedgehog pathway are involved in brainstem glioma. This may be related to the difference in malignant biological behavior between brainstem and hemispheric glioma and could be an ideal therapeutic target in brainstem glioma.
基金This work was supported by funds from the National Natural Science Foundation of China(31770840 to X.Ma and 31800989 to L.Xu)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(TP2017042 to X.Ma)。
文摘Non-alcoholic fatty liver disease(NAFLD)is a common chronic disease characterized by excessive fat accumulation in hepatocytes in the absence of alcohol consumption.Modern trends towards excessive calorie intake and sedentary life styles have increased the prevalence of NAFLD accompanied by obesity and type 2 diabetes.However,the molecular mechanisms underlying the initiation and progression of NAFLD are not clear.Zinc finger proteins(ZFPs)are a superfamily of metalloproteins that contain zinc finger motifs.ZFPs play diverse physiological roles in tissue homeostasis and also contribute to many pathological conditions,including metabolic,cardiovascular,and neurodegenerative diseases and various types of cancer.In this review,we highlight our current knowledge of several ZFPs that play critical roles in the progression of NAFLD,describe their mechanistic functional networks,and discuss the potential for ZFPs as therapeutic targets for NAFLD.
