Fizzy-related protein homolog 1 (FZR1) mainly functions as a specific activator of the anaphase-promotingcomplex/cyclosome (APC/C) in the cell cycle and controls the G0 and G1 phases of the cell cycle. We highlightrec...Fizzy-related protein homolog 1 (FZR1) mainly functions as a specific activator of the anaphase-promotingcomplex/cyclosome (APC/C) in the cell cycle and controls the G0 and G1 phases of the cell cycle. We highlightrecent work that has studied the role of FZR1 in tumorigenesis, growth, differentiation, and genome stability throughcell-cycle control. We summarize the current state of knowledge regarding FZR1 structure, function, and the distinctways of APC/C dysregulation in solid tumors and hematologic malignancies. We also discuss novel approaches fortargeting the FZR1 as a cancer therapy and research area for future work.展开更多
Background:Magnesium cantharidate(MC)is a protein phosphatase 2A(PP2A)inhibitor antitumor drug.However,its antitumor mechanism in hepatocellular carcinoma cell(HCC)remains unclear.Methods:PP2A lentiviral vector over e...Background:Magnesium cantharidate(MC)is a protein phosphatase 2A(PP2A)inhibitor antitumor drug.However,its antitumor mechanism in hepatocellular carcinoma cell(HCC)remains unclear.Methods:PP2A lentiviral vector over expression strategy was utilized both in vivo and in vitro to explore the antitumor effect in MC and okadaic acid(OA).Tumor weight was detected in mice after MC and OA exposure.Cell proliferation,cell cycle,apoptosis rate,and western blotting were detected to explore the effects on MC and OA in human hepatocarcinoma SMMC-7721 cells.Results:In vivo results demonstrated that MC inhibited HCC progression while OA promoted tumor growth.In vitro results demonstrated that MC effectively inhibited the growth of SMMC-7721 cells by arresting the cell cycle at the G2/M phase with inhibiting Cdc25C and activating the phosphorylation of the Cdc2 protein.Flow cytometry results further showed that MC increased apoptosis.Furthermore,the expression of phosphorylated ERK1/2 was lower in the MC group but higher in the OA group.Molecular docking results showed that MC docked well with ERK1/2.Conclusions:MC inhibited HCC progression by suppressing the growth and activating the apoptosis of cancer cells and suppressing the expression of PP2A and ERK1/2.展开更多
The mechanisms of testicular development in mammals are complex.Testis is an organ that produces sperm and secretes androgens.It is rich in exosomes and cytokines that mediate signal transduction between tubule germ c...The mechanisms of testicular development in mammals are complex.Testis is an organ that produces sperm and secretes androgens.It is rich in exosomes and cytokines that mediate signal transduction between tubule germ cells and distal cells,promoting testicular development and spermatogenesis.Exosomes are nanoscale extracellular vesicles that transmit information between cells.By transmitting information,exosomes play an important role in male infertility diseases such as azoospermia,varicocele,and testicular torsion.However,due to the wide range of sources of exosomes,extraction methods are numerous and complex.Therefore,there are many difficulties in studying the mechanisms of exosomal effects on normal development and male infertility.Therefore,in this review,first,we introduce the formation of exosomes and methods for culturing testis and sperm.Then,we introduce the effects of exosomes on different stages of testicular development.Finally,we summarize the prospects and shortcomings of exosomes when used in clinical applications.We lay the theoretical foundation for the mechanism of the influence of exosomes on normal development and male infertility.展开更多
基金Funding： This study was funded by the National Natural Science Foundation of China （81260488 and 81560669）, KeyLab Construction Project of the Educational Department of Guizhou Province （Project No. Guizhou EducationCooperation KY[2014]212） , Science Inovative Talent Team for Medicinal Insect Research and Development in Zunyi（Zunyi shi ke he 2015-40） and Modernization of Traditional Chinese Medicine in Guizhou Province high-tech researchand development projects （Qian ke he ZY 2012-2009）.
基金supported by the National Key Scientific Research Project(2017YFC1001903)Provincial and Ministerial Level Projects(cstc2016shmstzx10006)the Guizhou Provincial Science&Technology Program(QKHZC[2020]4Y154).
文摘Fizzy-related protein homolog 1 (FZR1) mainly functions as a specific activator of the anaphase-promotingcomplex/cyclosome (APC/C) in the cell cycle and controls the G0 and G1 phases of the cell cycle. We highlightrecent work that has studied the role of FZR1 in tumorigenesis, growth, differentiation, and genome stability throughcell-cycle control. We summarize the current state of knowledge regarding FZR1 structure, function, and the distinctways of APC/C dysregulation in solid tumors and hematologic malignancies. We also discuss novel approaches fortargeting the FZR1 as a cancer therapy and research area for future work.
基金The research was financially supported by the National Natural Science Foundation of China(no.81760746)Science and Technology Department of Zunyi city of Guizhou province of China([2020]7)Guizhou Provincial Science&Technology Program(ZK[2022]615).
文摘Background:Magnesium cantharidate(MC)is a protein phosphatase 2A(PP2A)inhibitor antitumor drug.However,its antitumor mechanism in hepatocellular carcinoma cell(HCC)remains unclear.Methods:PP2A lentiviral vector over expression strategy was utilized both in vivo and in vitro to explore the antitumor effect in MC and okadaic acid(OA).Tumor weight was detected in mice after MC and OA exposure.Cell proliferation,cell cycle,apoptosis rate,and western blotting were detected to explore the effects on MC and OA in human hepatocarcinoma SMMC-7721 cells.Results:In vivo results demonstrated that MC inhibited HCC progression while OA promoted tumor growth.In vitro results demonstrated that MC effectively inhibited the growth of SMMC-7721 cells by arresting the cell cycle at the G2/M phase with inhibiting Cdc25C and activating the phosphorylation of the Cdc2 protein.Flow cytometry results further showed that MC increased apoptosis.Furthermore,the expression of phosphorylated ERK1/2 was lower in the MC group but higher in the OA group.Molecular docking results showed that MC docked well with ERK1/2.Conclusions:MC inhibited HCC progression by suppressing the growth and activating the apoptosis of cancer cells and suppressing the expression of PP2A and ERK1/2.
基金supported by the National Nature Science Foundation of China(NSFC.No.31960156 and No.31660338)the Collaborative Innovation Center of Chinese Ministry of Education(2020-39)the High School Science and Technology Talent Support Project of Guizhou Province(QJH-KY-2016-079).
文摘The mechanisms of testicular development in mammals are complex.Testis is an organ that produces sperm and secretes androgens.It is rich in exosomes and cytokines that mediate signal transduction between tubule germ cells and distal cells,promoting testicular development and spermatogenesis.Exosomes are nanoscale extracellular vesicles that transmit information between cells.By transmitting information,exosomes play an important role in male infertility diseases such as azoospermia,varicocele,and testicular torsion.However,due to the wide range of sources of exosomes,extraction methods are numerous and complex.Therefore,there are many difficulties in studying the mechanisms of exosomal effects on normal development and male infertility.Therefore,in this review,first,we introduce the formation of exosomes and methods for culturing testis and sperm.Then,we introduce the effects of exosomes on different stages of testicular development.Finally,we summarize the prospects and shortcomings of exosomes when used in clinical applications.We lay the theoretical foundation for the mechanism of the influence of exosomes on normal development and male infertility.
