Insulin-like growth factor-I （IGF-I） plays a key role in female reproduction, because it has the effect of anti-apoptosis improving cell proliferation, transformation and differentiation. This paper reviewed the eff...Insulin-like growth factor-I （IGF-I） plays a key role in female reproduction, because it has the effect of anti-apoptosis improving cell proliferation, transformation and differentiation. This paper reviewed the effects of IGF-I on ovary, follicle growth, acquisition of oocyte competence and preimplantation embryo viability, and then summarized different points about IGF-1 for reproduction system展开更多
AIM: To investigate the molecular mechanisms of the high IGF-1 level linking diabetes and cancers, which is a risk factor.METHODS: We used cell growth, wound healing and transwell assay to evaluate the proliferation a...AIM: To investigate the molecular mechanisms of the high IGF-1 level linking diabetes and cancers, which is a risk factor.METHODS: We used cell growth, wound healing and transwell assay to evaluate the proliferation and metastasis ability of the hepatocellular carcinoma(HCC) cells. Western blot and reverse transcription polymerase chain reaction were used to assess a previously identified lysosomal protease, cathepsin B(CTSB) expression in the HCC cell lines. C57 BL/6J and KK-Ay diabetic mice are used to detect the growth and metastasis of HCC cells that were depleted with or without CTSB sh RNA in vivo. Statistical significance was determined by Student's t-test.RESULTS: IGF-1 promoted the growth and metastasis of the HCC cell lines via its ability to enhance CTSB expression in both a time-dependent and concentration-dependent manner. HCC cells grew much faster in diabetic KK-Ay mice than in C57 BL/6J mice. Additionally, more metastatic nodules were found in the lungs of KK-Ay mice than the lungs of C57 BL/6J mice. CTSB depletion protects against the tumorpromoting actions of IGF-1 in HCC cells, as well tumor growth and metastasis both in vitro and in vivo.IGF-1 did not change the m RNA levels of CTSB but prolonged the half-life of cathepsin B in Hepa 1-6 and H22 cells. Our results showed that IGF-1 promotes the growth and metastasis of the HCC cells most likely by hindering CTSB degradation mediated by the ubiquitinproteasome system(UPS), but not autophagy. Overexpression of proteasome activator 28, a family of activators of the 20 S proteasome, could not only restore IGF-1-inhibited UPS activity but also decrease IGF-1-induced CTSB accumulation.CONCLUSION: Our study demonstrates that IGF-1 promotes the growth and metastasis of hepatocellular carcinoma by inhibition of proteasome-mediated CTSB degradation.展开更多
Diabetes mellitus affects almost 350 million individuals throughout the globe resulting in sig-niifcant morbidity and mortality. Of further concern is the growing population of individuals that remain undiagnosed but ...Diabetes mellitus affects almost 350 million individuals throughout the globe resulting in sig-niifcant morbidity and mortality. Of further concern is the growing population of individuals that remain undiagnosed but are susceptible to the detrimental outcomes of this disorder. Dia-betes mellitus leads to multiple complications in the central and peripheral nervous systems that include cognitive impairment, retinal disease, neuropsychiatric disease, cerebral ischemia, and peripheral nerve degeneration. Although multiple strategies are being considered, novel target-ing of trophic factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1, and stem cell tissue regeneration are considered to be exciting prospects to overcome the cellular mechanisms that lead to neuronal injury in diabetes mellitus involving oxidative stress, apoptosis, and au-tophagy. Pathways that involve insulin-like growth factor-1, ifbroblast growth factor, epidermal growth factor, and erythropoietin can govern glucose homeostasis and are intimately tied to Wnt signaling that involves Wnt1 and Wnt1 inducible signaling pathway protein 1 （CCN4） to foster control over stem cell proliferation, wound repair, cognitive decline,β-cell proliferation, vascular regeneration, and programmed cell death. Ultimately, cellular metabolism through Wnt signal-ing is driven by primary metabolic pathways of the mechanistic target of rapamycin and AMP activated protein kinase. These pathways offer precise biological control of cellular metabolism, but are exquisitely sensitive to the different components of Wnt signaling. As a result, unexpected clinical outcomes can ensue and therefore demand careful translation of the mechanisms that govern neural repair and regeneration in diabetes mellitus.展开更多
The highest morbidity and mortality in the world are attributed to digestive system tumors,such as stomach cancer,liver cancer,and pancreatic cancer.Exploring potential biomarkers is a crucial direction of tumor resea...The highest morbidity and mortality in the world are attributed to digestive system tumors,such as stomach cancer,liver cancer,and pancreatic cancer.Exploring potential biomarkers is a crucial direction of tumor research.We use bioinformatics methods to explore potential biomarkers of the digestive system.Mining and analyzing data from Gene Expression Profiling Interactive Analysis(GEPIA),Kaplan-Meier,cBioPortal,and Metabolic gEne RApid Visualizer(MERAV)to explore the correlation between IGF2BP(insulin-like growth factor-2 mRNA-binding protein)family expression and immune infiltration in digestive system tumors,and further probe the prognostic value of IGF2BP family in digestive system tumors.Esophageal cancer tissues showed a significantly higher expression of IGF2BP2 than normal tissues,while IGF2BP3 was notably more expressed in esophageal cancer,pancreatic cancer,and stomach cancer.In the prognosis evaluation,the IGF2BP1 gene in patients with liver cancer and the IGF2BP2 and IGF2BP3 genes in patients with stomach cancer and liver cancer of the low gene expression level groups were better.Multivariate COX regression analysis further suggested that tumor stage,CD8 positive T cells,macrophages,dendritic cell infiltration,and IGF2BP3 expression were independent risk factors affecting the prognosis of patients with stem cell liver cancer.The IGF2BP family may be a potential marker for immunotherapy and the prognosis of digestive system tumors.展开更多
文摘Insulin-like growth factor-I （IGF-I） plays a key role in female reproduction, because it has the effect of anti-apoptosis improving cell proliferation, transformation and differentiation. This paper reviewed the effects of IGF-I on ovary, follicle growth, acquisition of oocyte competence and preimplantation embryo viability, and then summarized different points about IGF-1 for reproduction system
文摘AIM: To investigate the molecular mechanisms of the high IGF-1 level linking diabetes and cancers, which is a risk factor.METHODS: We used cell growth, wound healing and transwell assay to evaluate the proliferation and metastasis ability of the hepatocellular carcinoma(HCC) cells. Western blot and reverse transcription polymerase chain reaction were used to assess a previously identified lysosomal protease, cathepsin B(CTSB) expression in the HCC cell lines. C57 BL/6J and KK-Ay diabetic mice are used to detect the growth and metastasis of HCC cells that were depleted with or without CTSB sh RNA in vivo. Statistical significance was determined by Student's t-test.RESULTS: IGF-1 promoted the growth and metastasis of the HCC cell lines via its ability to enhance CTSB expression in both a time-dependent and concentration-dependent manner. HCC cells grew much faster in diabetic KK-Ay mice than in C57 BL/6J mice. Additionally, more metastatic nodules were found in the lungs of KK-Ay mice than the lungs of C57 BL/6J mice. CTSB depletion protects against the tumorpromoting actions of IGF-1 in HCC cells, as well tumor growth and metastasis both in vitro and in vivo.IGF-1 did not change the m RNA levels of CTSB but prolonged the half-life of cathepsin B in Hepa 1-6 and H22 cells. Our results showed that IGF-1 promotes the growth and metastasis of the HCC cells most likely by hindering CTSB degradation mediated by the ubiquitinproteasome system(UPS), but not autophagy. Overexpression of proteasome activator 28, a family of activators of the 20 S proteasome, could not only restore IGF-1-inhibited UPS activity but also decrease IGF-1-induced CTSB accumulation.CONCLUSION: Our study demonstrates that IGF-1 promotes the growth and metastasis of hepatocellular carcinoma by inhibition of proteasome-mediated CTSB degradation.
基金supported by the following grants to KM:American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Diabetes mellitus affects almost 350 million individuals throughout the globe resulting in sig-niifcant morbidity and mortality. Of further concern is the growing population of individuals that remain undiagnosed but are susceptible to the detrimental outcomes of this disorder. Dia-betes mellitus leads to multiple complications in the central and peripheral nervous systems that include cognitive impairment, retinal disease, neuropsychiatric disease, cerebral ischemia, and peripheral nerve degeneration. Although multiple strategies are being considered, novel target-ing of trophic factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1, and stem cell tissue regeneration are considered to be exciting prospects to overcome the cellular mechanisms that lead to neuronal injury in diabetes mellitus involving oxidative stress, apoptosis, and au-tophagy. Pathways that involve insulin-like growth factor-1, ifbroblast growth factor, epidermal growth factor, and erythropoietin can govern glucose homeostasis and are intimately tied to Wnt signaling that involves Wnt1 and Wnt1 inducible signaling pathway protein 1 （CCN4） to foster control over stem cell proliferation, wound repair, cognitive decline,β-cell proliferation, vascular regeneration, and programmed cell death. Ultimately, cellular metabolism through Wnt signal-ing is driven by primary metabolic pathways of the mechanistic target of rapamycin and AMP activated protein kinase. These pathways offer precise biological control of cellular metabolism, but are exquisitely sensitive to the different components of Wnt signaling. As a result, unexpected clinical outcomes can ensue and therefore demand careful translation of the mechanisms that govern neural repair and regeneration in diabetes mellitus.
基金from any funding agency in the public,commercial,or not-for-profit sectors.
文摘The highest morbidity and mortality in the world are attributed to digestive system tumors,such as stomach cancer,liver cancer,and pancreatic cancer.Exploring potential biomarkers is a crucial direction of tumor research.We use bioinformatics methods to explore potential biomarkers of the digestive system.Mining and analyzing data from Gene Expression Profiling Interactive Analysis(GEPIA),Kaplan-Meier,cBioPortal,and Metabolic gEne RApid Visualizer(MERAV)to explore the correlation between IGF2BP(insulin-like growth factor-2 mRNA-binding protein)family expression and immune infiltration in digestive system tumors,and further probe the prognostic value of IGF2BP family in digestive system tumors.Esophageal cancer tissues showed a significantly higher expression of IGF2BP2 than normal tissues,while IGF2BP3 was notably more expressed in esophageal cancer,pancreatic cancer,and stomach cancer.In the prognosis evaluation,the IGF2BP1 gene in patients with liver cancer and the IGF2BP2 and IGF2BP3 genes in patients with stomach cancer and liver cancer of the low gene expression level groups were better.Multivariate COX regression analysis further suggested that tumor stage,CD8 positive T cells,macrophages,dendritic cell infiltration,and IGF2BP3 expression were independent risk factors affecting the prognosis of patients with stem cell liver cancer.The IGF2BP family may be a potential marker for immunotherapy and the prognosis of digestive system tumors.
