Sexual dimorphism has been reported in various human diseases including autoimmune diseases,neurological diseases,pulmonary arterial hypertension,and some types of cancers,although the underlying mechanisms remain poo...Sexual dimorphism has been reported in various human diseases including autoimmune diseases,neurological diseases,pulmonary arterial hypertension,and some types of cancers,although the underlying mechanisms remain poorly understood.The long noncoding RNA(lncRNA)X-inactive specific transcript(XIST)is involved in X chromosome inactivation(XCI)in female placental mammals,a process that ensures the balanced expression dosage of X-linked genes between sexes.XIST is abnormally expressed in many sex-biased diseases.In addition,escape from XIST-mediated XCI and skewed XCI also contribute to sex-biased diseases.Therefore,its expression or modification can be regarded as a biomarker for the diagnosis and prognosis of many sex-biased diseases.Genetic manipulation of XIST expression can inhibit the progression of some of these diseases in animal models,and therefore XIST has been proposed as a potential therapeutic target.In this manuscript,we summarize the current knowledge about the mechanisms for XIST-mediated XCI and the roles of XIST in sex-biased diseases,and discuss potential therapeutic strategies targeting XIST.展开更多
基金This work was supported by the National Natural Science Foundation of China(No.32070870)Guangdong Basic and Applied Basic Research Foundation(No.2021A1515010758)+2 种基金Guangdong Provincial Key Laboratory of Synthetic Genomics,Shenzhen Key Laboratory of Synthetic Genomics(No.ZDSYS201802061806209)Shenzhen Institute of Synthetic Biology Scientific Research Program(No.ZTXM20200008 and DWKF20210003)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDPB18).
文摘Sexual dimorphism has been reported in various human diseases including autoimmune diseases,neurological diseases,pulmonary arterial hypertension,and some types of cancers,although the underlying mechanisms remain poorly understood.The long noncoding RNA(lncRNA)X-inactive specific transcript(XIST)is involved in X chromosome inactivation(XCI)in female placental mammals,a process that ensures the balanced expression dosage of X-linked genes between sexes.XIST is abnormally expressed in many sex-biased diseases.In addition,escape from XIST-mediated XCI and skewed XCI also contribute to sex-biased diseases.Therefore,its expression or modification can be regarded as a biomarker for the diagnosis and prognosis of many sex-biased diseases.Genetic manipulation of XIST expression can inhibit the progression of some of these diseases in animal models,and therefore XIST has been proposed as a potential therapeutic target.In this manuscript,we summarize the current knowledge about the mechanisms for XIST-mediated XCI and the roles of XIST in sex-biased diseases,and discuss potential therapeutic strategies targeting XIST.
