Background:Long non-coding RNAs(lncRNAs)plays an important role in the progression of gastric cancer(GC).Their involvement ranges from genetic regulation to cancer progression.However,the mechanistic roles of RP11-789...Background:Long non-coding RNAs(lncRNAs)plays an important role in the progression of gastric cancer(GC).Their involvement ranges from genetic regulation to cancer progression.However,the mechanistic roles of RP11-789C1.1 in GC are not fully understood.Methods:We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction.A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells.In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line.RNA pull-down unveiled RP11-789C1.1 interacting proteins.Western blot analysis indicated the downstream pathway changes of RP11-789C1.1,and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin.Results:Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells.Mechanistically,RP11-789C1.1 inhibited checkpoint kinase 1(CHK1)phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related(ATR),a serine/threonine-specific protein kinase,promoted GC apoptosis,and mediated oxaliplatin sensitivity.Conclusion:In general,we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action,providing a theoretical basis for targeted GC therapy.展开更多
The DNA damage response （DDR） is activated when DNA is altered by intrinsic or extrinsic agents. This pathway is a complex signaling network and plays important roles in genome stability, tumor transformation, and c...The DNA damage response （DDR） is activated when DNA is altered by intrinsic or extrinsic agents. This pathway is a complex signaling network and plays important roles in genome stability, tumor transformation, and cell cycle regulation. Human papillomaviruses （HPVs） are the main etiological agents of cervical cancer. Cervical cancer ranks as the fourth most common cancer among women and the second most frequent cause of cancer-related death worldwide. Over 200 types of HPVs have been identified and about one third of these infect the genital tract. The HPV life cycle is associated with epithelial differentiation. Recent studies have shown that HPVs deregulate the DDR to achieve a productive life cycle. In this review, I summarize current findings about how HPVs mediate the ataxia- telangiectasia mutated kinase （ATM） and the ATM- and RAD3-related kinase （ATR） DDRs, and focus on the roles that ATM and ATR signalings play in HPV viral replication. In addition, I demonstrate that the signal transducer and acti- vator of transcription-5 （STAT）-5, an important immune regulator, can promote ATM and ATR activations through different mechanisms. These findings may provide novel opportunities for development of new therapeutic targets for HPV-related cancers.展开更多
基金supported by the National Natural Science Foundation of China(No.81871908)Guangdong Provincial Natural Science Foundation(Nos.2018A030313715,2022A1515012202)+3 种基金Guangzhou Science and Technology plan-General Project(No.201904010036)Research Project Fund of Sun Yat-sen University(No.2015013)National Natural Science Foundation of China(No.82070529)General projects of Guangdong Provincial Natural Science Foundation(No.2021A1515010791).
文摘Background:Long non-coding RNAs(lncRNAs)plays an important role in the progression of gastric cancer(GC).Their involvement ranges from genetic regulation to cancer progression.However,the mechanistic roles of RP11-789C1.1 in GC are not fully understood.Methods:We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction.A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells.In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line.RNA pull-down unveiled RP11-789C1.1 interacting proteins.Western blot analysis indicated the downstream pathway changes of RP11-789C1.1,and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin.Results:Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells.Mechanistically,RP11-789C1.1 inhibited checkpoint kinase 1(CHK1)phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related(ATR),a serine/threonine-specific protein kinase,promoted GC apoptosis,and mediated oxaliplatin sensitivity.Conclusion:In general,we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action,providing a theoretical basis for targeted GC therapy.
文摘The DNA damage response （DDR） is activated when DNA is altered by intrinsic or extrinsic agents. This pathway is a complex signaling network and plays important roles in genome stability, tumor transformation, and cell cycle regulation. Human papillomaviruses （HPVs） are the main etiological agents of cervical cancer. Cervical cancer ranks as the fourth most common cancer among women and the second most frequent cause of cancer-related death worldwide. Over 200 types of HPVs have been identified and about one third of these infect the genital tract. The HPV life cycle is associated with epithelial differentiation. Recent studies have shown that HPVs deregulate the DDR to achieve a productive life cycle. In this review, I summarize current findings about how HPVs mediate the ataxia- telangiectasia mutated kinase （ATM） and the ATM- and RAD3-related kinase （ATR） DDRs, and focus on the roles that ATM and ATR signalings play in HPV viral replication. In addition, I demonstrate that the signal transducer and acti- vator of transcription-5 （STAT）-5, an important immune regulator, can promote ATM and ATR activations through different mechanisms. These findings may provide novel opportunities for development of new therapeutic targets for HPV-related cancers.
