胰腺癌是消化道常见的恶性肿瘤之一,由于发病隐匿,早期多无症状,被发现时多为疾病晚期,且部分患者已有周围组织侵犯及其他脏器转移,错过最佳手术时机,因此预后极差。胰腺癌诊断主要借助影像学及血清标志物检查,治疗方案是早期手术切除,...胰腺癌是消化道常见的恶性肿瘤之一,由于发病隐匿,早期多无症状,被发现时多为疾病晚期,且部分患者已有周围组织侵犯及其他脏器转移,错过最佳手术时机,因此预后极差。胰腺癌诊断主要借助影像学及血清标志物检查,治疗方案是早期手术切除,术后行一系列辅助治疗,但临床效果显示胰腺癌患者生存期仍较短。有研究表明,miR-429存在于胰腺癌组织及血液中,胰腺癌中还存在XIST/miR-429轴,在分子水平上,AFF3与X-非活性特异性转录本(X-inactive specific transcript,XIST)相关,但AFF3与胰腺癌相关的报道却十分罕见。本文对miR-429与AFF3进行介绍,预测它们可能是胰腺癌的治疗靶点,有望成为胰腺癌诊断及预后标志物。展开更多
X chromosome inactivation and genomic imprinting are two classic epigenetic regulatory processes that cause mono-allelic gene expression.In female mammals,mono-allelic expression of the long non-coding RNA gene X-inac...X chromosome inactivation and genomic imprinting are two classic epigenetic regulatory processes that cause mono-allelic gene expression.In female mammals,mono-allelic expression of the long non-coding RNA gene X-inactive specific transcript(XIST)is essential for initiation of X chromosome inactivation upon differentiation.We have previously demonstrated that the central factor of super elongation complex-like 3(SEC-L3),AFF3,is enriched at gamete differentially methylated regions(DMRs)of the imprinted loci and regulates the imprinted gene expression.Here,we found that AFF3 can also bind to the DMR downstream of the XIST promoter.Knockdown of AFF3 leads to de-repression of the inactive allele of X IST in terminally differentiated cells.In addition,the binding of AFF3 to the XIST DMR relies on DNA methylation and also regulates DNA methylation level at DMR region.However,the KAP1-H3K9 methylation machineries,which regulate the imprinted loci,might not play major roles in maintaining the mono-aUelic expression pattern of XIST in these cells.Thus,our results suggest that the differential mechanisms involved in the X IST DMR and gDMR regulation,which both require AFF3 and DNA methylation.展开更多
文摘胰腺癌是消化道常见的恶性肿瘤之一,由于发病隐匿,早期多无症状,被发现时多为疾病晚期,且部分患者已有周围组织侵犯及其他脏器转移,错过最佳手术时机,因此预后极差。胰腺癌诊断主要借助影像学及血清标志物检查,治疗方案是早期手术切除,术后行一系列辅助治疗,但临床效果显示胰腺癌患者生存期仍较短。有研究表明,miR-429存在于胰腺癌组织及血液中,胰腺癌中还存在XIST/miR-429轴,在分子水平上,AFF3与X-非活性特异性转录本(X-inactive specific transcript,XIST)相关,但AFF3与胰腺癌相关的报道却十分罕见。本文对miR-429与AFF3进行介绍,预测它们可能是胰腺癌的治疗靶点,有望成为胰腺癌诊断及预后标志物。
基金Thousand Young Talents Plan of China(5631006003 to C.L.,6231000011 to Z.L.)Natural Science Foundation of Jiangsu Province of China(BK20160026 to C.L.,BK20160666 and BK20170020 to Z.L.)Fundamental Research Funds for the Central Universities(3231007201 to C.L,3231008201 to Z.L.).
文摘X chromosome inactivation and genomic imprinting are two classic epigenetic regulatory processes that cause mono-allelic gene expression.In female mammals,mono-allelic expression of the long non-coding RNA gene X-inactive specific transcript(XIST)is essential for initiation of X chromosome inactivation upon differentiation.We have previously demonstrated that the central factor of super elongation complex-like 3(SEC-L3),AFF3,is enriched at gamete differentially methylated regions(DMRs)of the imprinted loci and regulates the imprinted gene expression.Here,we found that AFF3 can also bind to the DMR downstream of the XIST promoter.Knockdown of AFF3 leads to de-repression of the inactive allele of X IST in terminally differentiated cells.In addition,the binding of AFF3 to the XIST DMR relies on DNA methylation and also regulates DNA methylation level at DMR region.However,the KAP1-H3K9 methylation machineries,which regulate the imprinted loci,might not play major roles in maintaining the mono-aUelic expression pattern of XIST in these cells.Thus,our results suggest that the differential mechanisms involved in the X IST DMR and gDMR regulation,which both require AFF3 and DNA methylation.
