Endometriosis refers to as an estrogen-dependent disease.Estrogen receptorβ(ERB),the main estrogen receptor subtype which is encoded by the estrogen receptor 2(ESR2)gene,can mediate the action of estrogen in endometr...Endometriosis refers to as an estrogen-dependent disease.Estrogen receptorβ(ERB),the main estrogen receptor subtype which is encoded by the estrogen receptor 2(ESR2)gene,can mediate the action of estrogen in endometriosis.Although selective estrogen receptor modulators can target the ERβ,they are not specific due to the wide distribution of ERβ.Recently,long noncoding RNAs have been implicated in endometriosis.Therefore,we aim to explore and validate the downstream regulatory mechanism of ERβ,and to investigate the potential role of long intergenic noncoding RNA 1018(LINC01018)as a nonhormonal treatment for endometriosis.Our study demonstrates that the expression levels of ESR2 and LINCo1018 are increased in ectopic endometrial tissues and reveals a significant positive correlation between the ESR2 and LINCo1018 expression.Mechanistically,ERβdirectly binds to an estrogen response element located in the LINCO1018 promoter region and activates LINC01018 transcription.Functionally,ERβcan regulate the CDC25C/CDK1/CyclinB1 pathway and promote ectopic endometrial stromal cell proliferation via LINC01018 in vitro.Consistent with these findings,the knockdown of LINC01018 inhibits endometriotic lesion proliferation in vivo.In summary,our study demonstrates that the ERβ/LINC01018/CDC25C/CDK1/CyclinB1 signaling axis regulates endometriosis progression.展开更多
A recently identified protein,FAN1(FANCD2-associated nuclease 1,previously known as KIAA1018),is a novel nuclease associated with monoubiquitinated FANCD2 that is required for cellular resistance against DNA interstra...A recently identified protein,FAN1(FANCD2-associated nuclease 1,previously known as KIAA1018),is a novel nuclease associated with monoubiquitinated FANCD2 that is required for cellular resistance against DNA interstrand crosslinking(ICL)agents.The mechanisms of FAN1 regulation have not yet been explored.Here,we provide evidence that FAN1 is degraded during mitotic exit,suggesting that FAN1 may be a mitotic substrate of the anaphase-promoting cyclosome complex(APC/C).Indeed,Cdh1,but not Cdc20,was capable of regulating the protein level of FAN1 through the KEN box and the D-box.Moreover,the up-and down-regulation of FAN1 affected the progression to mitotic exit.Collectively,these data suggest that FAN1 may be a new mitotic substrate of APC/C Cdh1 that plays a key role during mitotic exit.展开更多
基金the National Natural Science Foundation of China(82271676)for funding support.
文摘Endometriosis refers to as an estrogen-dependent disease.Estrogen receptorβ(ERB),the main estrogen receptor subtype which is encoded by the estrogen receptor 2(ESR2)gene,can mediate the action of estrogen in endometriosis.Although selective estrogen receptor modulators can target the ERβ,they are not specific due to the wide distribution of ERβ.Recently,long noncoding RNAs have been implicated in endometriosis.Therefore,we aim to explore and validate the downstream regulatory mechanism of ERβ,and to investigate the potential role of long intergenic noncoding RNA 1018(LINC01018)as a nonhormonal treatment for endometriosis.Our study demonstrates that the expression levels of ESR2 and LINCo1018 are increased in ectopic endometrial tissues and reveals a significant positive correlation between the ESR2 and LINCo1018 expression.Mechanistically,ERβdirectly binds to an estrogen response element located in the LINCO1018 promoter region and activates LINC01018 transcription.Functionally,ERβcan regulate the CDC25C/CDK1/CyclinB1 pathway and promote ectopic endometrial stromal cell proliferation via LINC01018 in vitro.Consistent with these findings,the knockdown of LINC01018 inhibits endometriotic lesion proliferation in vivo.In summary,our study demonstrates that the ERβ/LINC01018/CDC25C/CDK1/CyclinB1 signaling axis regulates endometriosis progression.
基金supported by grants from Natural Science Foundation of Guangdong Province(No.10251008901000000 toT.K.)Ph.D.Program Foundation of Ministry of Education of China(No.20100171110079toT.K.)China Post doctoral Science Foundation(No.20110490966)
文摘A recently identified protein,FAN1(FANCD2-associated nuclease 1,previously known as KIAA1018),is a novel nuclease associated with monoubiquitinated FANCD2 that is required for cellular resistance against DNA interstrand crosslinking(ICL)agents.The mechanisms of FAN1 regulation have not yet been explored.Here,we provide evidence that FAN1 is degraded during mitotic exit,suggesting that FAN1 may be a mitotic substrate of the anaphase-promoting cyclosome complex(APC/C).Indeed,Cdh1,but not Cdc20,was capable of regulating the protein level of FAN1 through the KEN box and the D-box.Moreover,the up-and down-regulation of FAN1 affected the progression to mitotic exit.Collectively,these data suggest that FAN1 may be a new mitotic substrate of APC/C Cdh1 that plays a key role during mitotic exit.
