BACKGROUND Hepatocellular carcinoma(HCC) is one of the most common malignant tumors with high mortality-to-incidence ratios. Nuclear factor erythroid 2-like 3(NFE2 L3), also known as NRF3, is a member of the cap ‘n&#...BACKGROUND Hepatocellular carcinoma(HCC) is one of the most common malignant tumors with high mortality-to-incidence ratios. Nuclear factor erythroid 2-like 3(NFE2 L3), also known as NRF3, is a member of the cap ‘n' collar basic-region leucine zipper family of transcription factors. NFE2 L3 is involved in the regulation of various biological processes, whereas its role in HCC has not been elucidated.AIM To explore the expression and biological function of NFE2 L3 in HCC.METHODS We analyzed the expression of NFE2 L3 in HCC tissues and its correlation with clinicopathological parameters based on The Cancer Genome Atlas(TCGA) data portal. Short hairpin RNA(shRNA) interference technology was utilized to knock down NFE2 L3 in vitro. Cell apoptosis, clone formation, proliferation, migration,and invasion assays were used to identify the biological effects of NFE2 L3 in BEL-7404 and SMMC-7721 cells. The expression of epithelial-mesenchymal transition(EMT) markers was examined by Western blot analysis.RESULTS TCGA analysis showed that NFE2 L3 expression was significantly positively correlated with tumor grade, T stage, and pathologic stage. The qPCR and Western blot results showed that both the mRNA and protein levels of NFE2 L3 were significantly decreased after shRNA-mediated knockdown in BEL-7404 and SMMC-7721 cells. The shRNA-mediated knockdown of NFE2 L3 could induce apoptosis and inhibit the clone formation and cell proliferation of SMMC-7721 and BEL-7404 cells. NFE2 L3 knockdown also significantly suppressed the migration, invasion, and EMT of the two cell lines.CONCLUSION Our study showed that shRNA-mediated knockdown of NFE2 L3 exhibited tumor-suppressing effects in HCC cells.展开更多
Redox balance is fundamentally important for physiological homeostasis. Pathological factors that disturb this dedicated balance may result in oxidative stress, leading to the development or aggravation of a variety o...Redox balance is fundamentally important for physiological homeostasis. Pathological factors that disturb this dedicated balance may result in oxidative stress, leading to the development or aggravation of a variety of diseases, including diabetes mellitus, cardiovascular diseases, metabolic syndrome as well as inflammation, aging and cancer. Thus, the capacity of endogenous free radical clearance can be of patho-physiological importance; in this regard, the major reactive oxygen species defense machinery, the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) system needs to be precisely modulated in response to pathological alterations. While oxidative stress is among the early events that lead to the development of insulin resistance, the activation of Nrf2 scavenging capacity leads to insulin sensitization. Furthermore, Nrf2 is evidently involved in regulating lipid metabolism. Here we summarize recent findings that link the Nrf2 system to metabolic homeostasis and insulin action and present our view that Nrf2 may serve as a novel drug target for diabetes and its complications.展开更多
5-Aminolevulinic acid(ALA)can inhibit abscisic acid(ABA)-induced stomatal closure.However,the molecular mechanism is unclear.In this study,we found that ALA upregulated the MdPP2AC expression and PP2A activity in the ...5-Aminolevulinic acid(ALA)can inhibit abscisic acid(ABA)-induced stomatal closure.However,the molecular mechanism is unclear.In this study,we found that ALA upregulated the MdPP2AC expression and PP2A activity in the apple(Malus domestica Borkh.cv.‘Fuji’)leaves.With the promoter of MdPP2AC as bait,a diacylglycerol kinase MdDGK3-like was selected by the Yeast One Hybrid(Y1H)from the cDNA library of the epidermis of apple leaves treated by exogenous ALA.Additional to binding the promoter of MdPP2AC,MdDGK3-like was found to inhibit the transcription activity of MdPP2AC promoter,while ALA significantly eliminated the role of MdDGK3-like.In tobacco leaves,MdDGK3-like was localized in the nucleus of stomatal guard cells.Therefore,MdDGK3-like might act as a transcription factor negatively regulating MdPP2AC expression and causing stomatal closure.To further identify MdDGK3-like functions,several transiently transgenic apple leaves(including overexpression and interference)were established.The results revealed that overexpression of MdDGK3-like promoted stomatal closure by increasing Ca^(2+)and H_(2)O_(2)and decreasing flavonol levels in the guard cells.Conversely,MdDGK3-like(i)led the stomatal opening with lower levels of Ca^(2+)and H_(2)O_(2)but higher flavonols.Based on these,we proposed a new hypothesis that ALA up-regulated MdPP2AC expression via negatively regulating the expression of MdDGK3-like to up-regulate PP2A expression and the enzyme activity,which improved the stomatal aperture.Since it was the first time that MdDGK3-like was showed to act as a transcription factor,the proposed model provided a new insight onto the mechanisms of ALA-induced stomatal opening.展开更多
基金the Changzhou High-Level Medical Talents Training Project,No.2016ZCLJ002
文摘BACKGROUND Hepatocellular carcinoma(HCC) is one of the most common malignant tumors with high mortality-to-incidence ratios. Nuclear factor erythroid 2-like 3(NFE2 L3), also known as NRF3, is a member of the cap ‘n' collar basic-region leucine zipper family of transcription factors. NFE2 L3 is involved in the regulation of various biological processes, whereas its role in HCC has not been elucidated.AIM To explore the expression and biological function of NFE2 L3 in HCC.METHODS We analyzed the expression of NFE2 L3 in HCC tissues and its correlation with clinicopathological parameters based on The Cancer Genome Atlas(TCGA) data portal. Short hairpin RNA(shRNA) interference technology was utilized to knock down NFE2 L3 in vitro. Cell apoptosis, clone formation, proliferation, migration,and invasion assays were used to identify the biological effects of NFE2 L3 in BEL-7404 and SMMC-7721 cells. The expression of epithelial-mesenchymal transition(EMT) markers was examined by Western blot analysis.RESULTS TCGA analysis showed that NFE2 L3 expression was significantly positively correlated with tumor grade, T stage, and pathologic stage. The qPCR and Western blot results showed that both the mRNA and protein levels of NFE2 L3 were significantly decreased after shRNA-mediated knockdown in BEL-7404 and SMMC-7721 cells. The shRNA-mediated knockdown of NFE2 L3 could induce apoptosis and inhibit the clone formation and cell proliferation of SMMC-7721 and BEL-7404 cells. NFE2 L3 knockdown also significantly suppressed the migration, invasion, and EMT of the two cell lines.CONCLUSION Our study showed that shRNA-mediated knockdown of NFE2 L3 exhibited tumor-suppressing effects in HCC cells.
基金Supported by An operating grant from Canadian Institutes of Health Research,No.89887 to Jin TRa NSFC grant,No.81072300 to Jin TR and Yu ZWa NSFC grant,No.30730079 to Ling WH in part
文摘Redox balance is fundamentally important for physiological homeostasis. Pathological factors that disturb this dedicated balance may result in oxidative stress, leading to the development or aggravation of a variety of diseases, including diabetes mellitus, cardiovascular diseases, metabolic syndrome as well as inflammation, aging and cancer. Thus, the capacity of endogenous free radical clearance can be of patho-physiological importance; in this regard, the major reactive oxygen species defense machinery, the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) system needs to be precisely modulated in response to pathological alterations. While oxidative stress is among the early events that lead to the development of insulin resistance, the activation of Nrf2 scavenging capacity leads to insulin sensitization. Furthermore, Nrf2 is evidently involved in regulating lipid metabolism. Here we summarize recent findings that link the Nrf2 system to metabolic homeostasis and insulin action and present our view that Nrf2 may serve as a novel drug target for diabetes and its complications.
基金supported by the National Natural Science Foundation of China(Grant No.32172512)the Jiangsu Special Fund for Frontier Foundation Research of Carbon Peaking and Carbon Neutralization(Grant No.BK20220005)+1 种基金Jiangsu Agricultural Science and Technology Innovation Fund[Grant No.CX(20)2023]a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘5-Aminolevulinic acid(ALA)can inhibit abscisic acid(ABA)-induced stomatal closure.However,the molecular mechanism is unclear.In this study,we found that ALA upregulated the MdPP2AC expression and PP2A activity in the apple(Malus domestica Borkh.cv.‘Fuji’)leaves.With the promoter of MdPP2AC as bait,a diacylglycerol kinase MdDGK3-like was selected by the Yeast One Hybrid(Y1H)from the cDNA library of the epidermis of apple leaves treated by exogenous ALA.Additional to binding the promoter of MdPP2AC,MdDGK3-like was found to inhibit the transcription activity of MdPP2AC promoter,while ALA significantly eliminated the role of MdDGK3-like.In tobacco leaves,MdDGK3-like was localized in the nucleus of stomatal guard cells.Therefore,MdDGK3-like might act as a transcription factor negatively regulating MdPP2AC expression and causing stomatal closure.To further identify MdDGK3-like functions,several transiently transgenic apple leaves(including overexpression and interference)were established.The results revealed that overexpression of MdDGK3-like promoted stomatal closure by increasing Ca^(2+)and H_(2)O_(2)and decreasing flavonol levels in the guard cells.Conversely,MdDGK3-like(i)led the stomatal opening with lower levels of Ca^(2+)and H_(2)O_(2)but higher flavonols.Based on these,we proposed a new hypothesis that ALA up-regulated MdPP2AC expression via negatively regulating the expression of MdDGK3-like to up-regulate PP2A expression and the enzyme activity,which improved the stomatal aperture.Since it was the first time that MdDGK3-like was showed to act as a transcription factor,the proposed model provided a new insight onto the mechanisms of ALA-induced stomatal opening.
