目的探讨miR-101和RanBP9在隐睾睾丸组织中的表达情况及其可能作用。方法取60只雄性6周龄ICR小鼠,随机选取30只进行左侧隐睾造模手术,视为隐睾组(Cry组),右侧睾丸位于阴囊内,视为自身对照组(SC组);另外30只进行假手术后睾丸仍位于阴囊内...目的探讨miR-101和RanBP9在隐睾睾丸组织中的表达情况及其可能作用。方法取60只雄性6周龄ICR小鼠,随机选取30只进行左侧隐睾造模手术,视为隐睾组(Cry组),右侧睾丸位于阴囊内,视为自身对照组(SC组);另外30只进行假手术后睾丸仍位于阴囊内,视为假手术组(Con组)。小鼠根据手术后时间随机分为5组,每组包含6只隐睾组小鼠和6只假手术组小鼠,分别于术后3、7、14、21、28 d处死小鼠。称量小鼠体质量、睾丸重量,睾丸进行HE染色观察组织形态学改变,qRT-PCR检测miR-101表达水平,Western blot、qRT-PCR和免疫荧光用于检测RanBP9的表达变化情况。结果与假手术组及自身右侧睾丸对照相比,隐睾组小鼠左侧睾丸在术后7 d出现结构损坏,且睾丸体质量比出现明显下降( P <0.05);miR-101在隐睾中表达增加而RanBP9的表达减少( P <0.05)。结论隐睾中miR-101表达增加而RanBP9表达量减少,这可能是隐睾中精子发生障碍的原因之一。展开更多
Non-small cell lung cancer(NSCLC)remains the leading cause of cancer-related deaths in the Western world.Despite progress made with targeted therapies and immune checkpoint inhibitors,the vast majority of patients hav...Non-small cell lung cancer(NSCLC)remains the leading cause of cancer-related deaths in the Western world.Despite progress made with targeted therapies and immune checkpoint inhibitors,the vast majority of patients have to undergo chemotherapy with platinum-based drugs.To increase efficacy and reduce potential side effects,a more comprehensive understanding of the mechanisms of the DNA damage response(DDR)is required.We have shown that overexpressby live cell imaging Incuyion of the scaffold protein RAN binding protein 9(RANBP9)is pervasive in NSCLC.More importantly,patients with higher levels of RANBP9 exhibit a worse outcome from treatment with platinum-based drugs.Mechanistically,RANBP9 exists as a target and an enabler of the ataxia telangiectasia mutated(ATM)kinase signaling.Indeed,the depletion of RANBP9 in NSCLC cells abates ATM activation and its downstream targets such as pby live cell imaging Incuy53 signaling.RANBP9 knockout cells are more sensitive than controls to the inhibition of the ataxia and telangiectasia-related(ATR)kinase but not to ATM inhibition.The absence of RANBP9 renders cells more sensitive to drugs inhibiting the Poly(ADP-ribose)-Polymerase(PARP)resulting in a“BRCAness-like”phenotype.In summary,as a result of increased sensitivity to DNA damaging drugs conferred by its ablation in vitro and in vivo,RANBP9 may be considered as a potential target for the treatment of NSCLC.This article aims to report the results from past and ongoing investigations focused on the role of RANBP9 in the response to DNA damage,particularly in the context of NSCLC.This review concludes with future directions and speculative remarks which will need to be addressed in the coming years.展开更多
文摘目的探讨miR-101和RanBP9在隐睾睾丸组织中的表达情况及其可能作用。方法取60只雄性6周龄ICR小鼠,随机选取30只进行左侧隐睾造模手术,视为隐睾组(Cry组),右侧睾丸位于阴囊内,视为自身对照组(SC组);另外30只进行假手术后睾丸仍位于阴囊内,视为假手术组(Con组)。小鼠根据手术后时间随机分为5组,每组包含6只隐睾组小鼠和6只假手术组小鼠,分别于术后3、7、14、21、28 d处死小鼠。称量小鼠体质量、睾丸重量,睾丸进行HE染色观察组织形态学改变,qRT-PCR检测miR-101表达水平,Western blot、qRT-PCR和免疫荧光用于检测RanBP9的表达变化情况。结果与假手术组及自身右侧睾丸对照相比,隐睾组小鼠左侧睾丸在术后7 d出现结构损坏,且睾丸体质量比出现明显下降( P <0.05);miR-101在隐睾中表达增加而RanBP9的表达减少( P <0.05)。结论隐睾中miR-101表达增加而RanBP9表达量减少,这可能是隐睾中精子发生障碍的原因之一。
基金the Ohio State University Comprehensive Cancer Center(P30 CA016058).
文摘Non-small cell lung cancer(NSCLC)remains the leading cause of cancer-related deaths in the Western world.Despite progress made with targeted therapies and immune checkpoint inhibitors,the vast majority of patients have to undergo chemotherapy with platinum-based drugs.To increase efficacy and reduce potential side effects,a more comprehensive understanding of the mechanisms of the DNA damage response(DDR)is required.We have shown that overexpressby live cell imaging Incuyion of the scaffold protein RAN binding protein 9(RANBP9)is pervasive in NSCLC.More importantly,patients with higher levels of RANBP9 exhibit a worse outcome from treatment with platinum-based drugs.Mechanistically,RANBP9 exists as a target and an enabler of the ataxia telangiectasia mutated(ATM)kinase signaling.Indeed,the depletion of RANBP9 in NSCLC cells abates ATM activation and its downstream targets such as pby live cell imaging Incuy53 signaling.RANBP9 knockout cells are more sensitive than controls to the inhibition of the ataxia and telangiectasia-related(ATR)kinase but not to ATM inhibition.The absence of RANBP9 renders cells more sensitive to drugs inhibiting the Poly(ADP-ribose)-Polymerase(PARP)resulting in a“BRCAness-like”phenotype.In summary,as a result of increased sensitivity to DNA damaging drugs conferred by its ablation in vitro and in vivo,RANBP9 may be considered as a potential target for the treatment of NSCLC.This article aims to report the results from past and ongoing investigations focused on the role of RANBP9 in the response to DNA damage,particularly in the context of NSCLC.This review concludes with future directions and speculative remarks which will need to be addressed in the coming years.
