Inflammation is indispensable for host defense,whereas excessive inflammation often develop inflammatory diseases.Autophagy is thought to be engaged in many extracellular stress responses,such as starvation and innate...Inflammation is indispensable for host defense,whereas excessive inflammation often develop inflammatory diseases.Autophagy is thought to be engaged in many extracellular stress responses,such as starvation and innate immunity.Thus,autophagy plays an important role in maintaining homeostasis.The purpose of this study was to elucidate the function of BRF1 in the regulation of inflammation and autophagy response in macrophages.We found that BRF1 inhibited the LPS-induced inflammatory factors expression and the autophagy flux in macrophage.Furthermore,inhibition autophagy with 3-MA can attenuate the suppressive effect of BRF1 on LPS-mediated inflammation.In addition,MAPK/ERK signaling pathway was involved in the BRF1 inhibition inflammation and autophagy in macrophages.These findings indicate that BRF1 attenuates LPS-induced inflammatory factors secretion through autophagy,at least in part,through MAPK/ERK signaling pathway.展开更多
The levels of the products of RNA polymeraseⅢ-dependent genes(PolⅢgenes),including tRNAs and 5S rRNA,are elevated in transformed and tumor cells,which potentiate tumorigenesis.TFIIB-related factor 1(Brf1)is a key tr...The levels of the products of RNA polymeraseⅢ-dependent genes(PolⅢgenes),including tRNAs and 5S rRNA,are elevated in transformed and tumor cells,which potentiate tumorigenesis.TFIIB-related factor 1(Brf1)is a key transcription factor and specifically regulates the transcription of PolⅢgenes.In vivo and in vitro studies have demonstrated that a decrease in Brf1 reduces PolⅢgene transcription and is sufficient for inhibiting cell transformation and tumor formation.Emerging evidence indicates that dysregulation of Brf1 and PolⅢgenes is linked to the development of hepatocellular carcinoma(HCC)in humans and animals.We have reported that Brf1 is overexpressed in human liver cancer patients and that those with high Brf1 levels have shorter survivals.This review summarizes the effects of dysregulation of these genes on HCC and their regulation by signaling pathways and epigenetics.These novel data should help us determine the molecular mechanisms of HCC from a different perspective and guide the development of therapeutic approaches for HCC patients.展开更多
基金supported by the National Natural Science Foundation of China(81672209).
文摘Inflammation is indispensable for host defense,whereas excessive inflammation often develop inflammatory diseases.Autophagy is thought to be engaged in many extracellular stress responses,such as starvation and innate immunity.Thus,autophagy plays an important role in maintaining homeostasis.The purpose of this study was to elucidate the function of BRF1 in the regulation of inflammation and autophagy response in macrophages.We found that BRF1 inhibited the LPS-induced inflammatory factors expression and the autophagy flux in macrophage.Furthermore,inhibition autophagy with 3-MA can attenuate the suppressive effect of BRF1 on LPS-mediated inflammation.In addition,MAPK/ERK signaling pathway was involved in the BRF1 inhibition inflammation and autophagy in macrophages.These findings indicate that BRF1 attenuates LPS-induced inflammatory factors secretion through autophagy,at least in part,through MAPK/ERK signaling pathway.
基金This work was supported in part by NIAAA/NIH grants AA017288,AA021114,AA023247,and AA024169 to SZ.
文摘The levels of the products of RNA polymeraseⅢ-dependent genes(PolⅢgenes),including tRNAs and 5S rRNA,are elevated in transformed and tumor cells,which potentiate tumorigenesis.TFIIB-related factor 1(Brf1)is a key transcription factor and specifically regulates the transcription of PolⅢgenes.In vivo and in vitro studies have demonstrated that a decrease in Brf1 reduces PolⅢgene transcription and is sufficient for inhibiting cell transformation and tumor formation.Emerging evidence indicates that dysregulation of Brf1 and PolⅢgenes is linked to the development of hepatocellular carcinoma(HCC)in humans and animals.We have reported that Brf1 is overexpressed in human liver cancer patients and that those with high Brf1 levels have shorter survivals.This review summarizes the effects of dysregulation of these genes on HCC and their regulation by signaling pathways and epigenetics.These novel data should help us determine the molecular mechanisms of HCC from a different perspective and guide the development of therapeutic approaches for HCC patients.
