Dear Editor,The COVID-19 pandemic caused by SARS-CoV-2 has led to acute respiratory distress syndrome(ARDS)with a high rate of death.An excessive inflammatory response,caused by virus infection,is associated with seve...Dear Editor,The COVID-19 pandemic caused by SARS-CoV-2 has led to acute respiratory distress syndrome(ARDS)with a high rate of death.An excessive inflammatory response,caused by virus infection,is associated with severe clinical manifestations that may lead to death of patients.1 Therefore,the blockage of virus replication and suppression of hyper-inflammatory response are beneficial for COVID-19 treatment.However,the drug targeting both virus and hyper-inflammation,as far as we know,is not available yet.展开更多
TERC is the RNA component of telomerase,and provides a template for TERT to synthesize telomere repeats at chromosome ends.Increasing evidence has revealed that TERC is involved in other biological processes beyond te...TERC is the RNA component of telomerase,and provides a template for TERT to synthesize telomere repeats at chromosome ends.Increasing evidence has revealed that TERC is involved in other biological processes beyond telomerase.Here,we found that the expression level of TERC is negatively correlated with PD-L1 and that ectopic expression of TERC but not TERT in ALT cells significantly inhibits PD-L1,suggesting that TERC suppresses PD-L1 expression in a telomerase-independent manner.Mechanistically,instead of regulating PD-L1 m RNA directly,TERC accelerates PD-L1 m RNA degradation by inhibiting the expression of Hu R,which binds to the 3′UTR of PD-L1 m RNA and maintains its stability.We also found that the small molecule AS1842856,a Fox O1 inhibitor,promotes TERC expression and reverses the PD-L1 upregulation caused by chemotherapy,providing a potential combination cancer therapy that avoids cancer immune escape during chemotherapy.展开更多
Professor Yong Zhao was the Dean of School of Life Sciences at Sun Yat-sen University and a renowned biologist whose studies focused on the role of telomeres and telom-erase in cancer and aging.Dr.Zhao's postdocto...Professor Yong Zhao was the Dean of School of Life Sciences at Sun Yat-sen University and a renowned biologist whose studies focused on the role of telomeres and telom-erase in cancer and aging.Dr.Zhao's postdoctoral mentor Professor Woodring E.Wright(1949-2019)of University of Texas Southwestern Medical Center(UTSW)once remarked,“It will be hard for anyone else in my lab to match up to the superb performance of Yong Zhao.”展开更多
基金supported by National Key R&D Program of China[2018YFA0107000]National Natural Science Foundation of China Grants(82025014,31900516,8201101103,81870506,and 21701194)+3 种基金Guangzhou Municipal People's Livelihood Science and technology plan[201803010108]Fundamental Research Funds for Central Universities(20lgpy119,19lgpy177)the China Postdoctoral Science Foundation(2019M653170)Shenzhen Key Medical Discipline Construction Fund(SZXK002)and grant from COVID-19 emergency tackling research project of Shandong University(Grant No.2020XGB03 to P.H.W).
文摘Dear Editor,The COVID-19 pandemic caused by SARS-CoV-2 has led to acute respiratory distress syndrome(ARDS)with a high rate of death.An excessive inflammatory response,caused by virus infection,is associated with severe clinical manifestations that may lead to death of patients.1 Therefore,the blockage of virus replication and suppression of hyper-inflammatory response are beneficial for COVID-19 treatment.However,the drug targeting both virus and hyper-inflammation,as far as we know,is not available yet.
基金supported by the National Natural Science Foundation of China(31970683,82171549)Guangdong Basic and Applied Basic Research Foundation(2021A1515010848)。
文摘TERC is the RNA component of telomerase,and provides a template for TERT to synthesize telomere repeats at chromosome ends.Increasing evidence has revealed that TERC is involved in other biological processes beyond telomerase.Here,we found that the expression level of TERC is negatively correlated with PD-L1 and that ectopic expression of TERC but not TERT in ALT cells significantly inhibits PD-L1,suggesting that TERC suppresses PD-L1 expression in a telomerase-independent manner.Mechanistically,instead of regulating PD-L1 m RNA directly,TERC accelerates PD-L1 m RNA degradation by inhibiting the expression of Hu R,which binds to the 3′UTR of PD-L1 m RNA and maintains its stability.We also found that the small molecule AS1842856,a Fox O1 inhibitor,promotes TERC expression and reverses the PD-L1 upregulation caused by chemotherapy,providing a potential combination cancer therapy that avoids cancer immune escape during chemotherapy.
文摘Professor Yong Zhao was the Dean of School of Life Sciences at Sun Yat-sen University and a renowned biologist whose studies focused on the role of telomeres and telom-erase in cancer and aging.Dr.Zhao's postdoctoral mentor Professor Woodring E.Wright(1949-2019)of University of Texas Southwestern Medical Center(UTSW)once remarked,“It will be hard for anyone else in my lab to match up to the superb performance of Yong Zhao.”
