目的研究膀胱癌中,RASSF2A、NORE1A基因启动子甲基化状态在肿瘤发生发展中的作用。方法采用甲基化特异性PCR(methylation specific PCR,MSP)技术检测54例膀胱癌组织及其相应癌周正常组织RASSF2A、NORE1A基因启动子甲基化状态。结果(1)RA...目的研究膀胱癌中,RASSF2A、NORE1A基因启动子甲基化状态在肿瘤发生发展中的作用。方法采用甲基化特异性PCR(methylation specific PCR,MSP)技术检测54例膀胱癌组织及其相应癌周正常组织RASSF2A、NORE1A基因启动子甲基化状态。结果(1)RASSF2A检出率仅为2/54,NORE1A仅为0/54;(2)相应癌周正常组织和3例正常膀胱组织均未发现该基因高甲基化改变;(3)甲基化状态与膀胱癌临床病理参数无明显相关性。结论RASSF2A、NORE1A在膀胱肿瘤中的甲基化率较低,并不适合进行临床筛查。展开更多
Loss of the RASSF2A expression induced by methylation-mediated silencing has been reported in several human cancers, but the methylation status of RASSF2A in hepatocellular carcinoma （HCC） is rarely studied so far. ...Loss of the RASSF2A expression induced by methylation-mediated silencing has been reported in several human cancers, but the methylation status of RASSF2A in hepatocellular carcinoma （HCC） is rarely studied so far. In this study, we investigated the RASSF2A expression and its methylation status in a cohort of 45 hepatitis B virus-associated HCC tissues and their adjacent non-carcinoma tissues by using RT-PCR and MS-PCR. Promoter methylation of RASSF2A was found in 31 （68.9%） out of 45 HCC tissues and 12 （40%） out of 30 adjacent normal tissues, respectively （P〈0.05）. The methylation status of PASSF2A was closely associated with the loss of RASSF2A expression and elevated serum α-fetoprotein level, but not significantly with clinical stage, hepatic fibrosis and K-ras mutation. It was concluded that aberrant methylation of the RASSF2A gene with the subsequent loss of RASSF2A expression plays an important role in the pathogenesis of HCC.展开更多
Sensory hair cells are responsible for detecting and transmitting sound in the inner ear,and damage to HCs leads to hearing loss.HCs do not regenerate spontaneously in adult mammals,which makes the hearing loss perman...Sensory hair cells are responsible for detecting and transmitting sound in the inner ear,and damage to HCs leads to hearing loss.HCs do not regenerate spontaneously in adult mammals,which makes the hearing loss permanent.However,hair cells and supporting cells have the same precursors in the inner ear,and in newborn mice,the adjacent SCs can be activated by gene manipulation to differentiate into newly regenerated hair cells.Here,we demonstrate the role of the Ras association domain family member 2(Rassf2)in supporting cell to hair cell trans-differentiation in the inner ear.Using the AAV vector(AAV-ie)to upregulate Rassf2 expression promoted supporting cell division and hair cell production in cultured cochlear organoids.Also,AAV-Rassf2 enhanced the regenerative ability of Lgr5+SCs in the postnatal cochlea without impairing hearing,and this might due to the modulation of the Wnt,Hedgehog and Notch signaling pathways.Furthermore,AAV-Rassf2 enhances cochlear supporting cell division and hair cell production in the neomycin injury model.In summary,our results suggest that Rassf2 is a key component in HC regenerative repair,and gene modulation mediated by adeno-associated virus may be a promising gene therapy for hearing repair.展开更多
文摘目的研究膀胱癌中,RASSF2A、NORE1A基因启动子甲基化状态在肿瘤发生发展中的作用。方法采用甲基化特异性PCR(methylation specific PCR,MSP)技术检测54例膀胱癌组织及其相应癌周正常组织RASSF2A、NORE1A基因启动子甲基化状态。结果(1)RASSF2A检出率仅为2/54,NORE1A仅为0/54;(2)相应癌周正常组织和3例正常膀胱组织均未发现该基因高甲基化改变;(3)甲基化状态与膀胱癌临床病理参数无明显相关性。结论RASSF2A、NORE1A在膀胱肿瘤中的甲基化率较低,并不适合进行临床筛查。
文摘Loss of the RASSF2A expression induced by methylation-mediated silencing has been reported in several human cancers, but the methylation status of RASSF2A in hepatocellular carcinoma （HCC） is rarely studied so far. In this study, we investigated the RASSF2A expression and its methylation status in a cohort of 45 hepatitis B virus-associated HCC tissues and their adjacent non-carcinoma tissues by using RT-PCR and MS-PCR. Promoter methylation of RASSF2A was found in 31 （68.9%） out of 45 HCC tissues and 12 （40%） out of 30 adjacent normal tissues, respectively （P〈0.05）. The methylation status of PASSF2A was closely associated with the loss of RASSF2A expression and elevated serum α-fetoprotein level, but not significantly with clinical stage, hepatic fibrosis and K-ras mutation. It was concluded that aberrant methylation of the RASSF2A gene with the subsequent loss of RASSF2A expression plays an important role in the pathogenesis of HCC.
基金supported by the National Key Research and Development Program of China (2021YFA1101300,2020YFA0112503,2021YFA1101800 and 2020YFA0113600)the National Natural Science Foundation of China (81970882,82030029,92149304,82000984 and 82171146)+6 种基金the China National Postdoctoral Program for Innovative Talents (BX20200082)the China Postdoctoral Science Foundation (2020M681468)the Science and Technology Department of Sichuan Province (2021YFS0371)the Shenzhen Fundamental Research Pro-gram (JCYJ20190814093401920 and JCYJ20210324125608022)the Open Research Fund of State Key Laboratory of Genetic Engineering,Fudan University (SKLGE-2104)2022 Open Project Fund of Guangdong Academy of Medical Sciences to P.N.W. (YKY-KF202201)Key Program of Zhejiang Provincial Natural Science Foundation of China (LZ22H130001).
文摘Sensory hair cells are responsible for detecting and transmitting sound in the inner ear,and damage to HCs leads to hearing loss.HCs do not regenerate spontaneously in adult mammals,which makes the hearing loss permanent.However,hair cells and supporting cells have the same precursors in the inner ear,and in newborn mice,the adjacent SCs can be activated by gene manipulation to differentiate into newly regenerated hair cells.Here,we demonstrate the role of the Ras association domain family member 2(Rassf2)in supporting cell to hair cell trans-differentiation in the inner ear.Using the AAV vector(AAV-ie)to upregulate Rassf2 expression promoted supporting cell division and hair cell production in cultured cochlear organoids.Also,AAV-Rassf2 enhanced the regenerative ability of Lgr5+SCs in the postnatal cochlea without impairing hearing,and this might due to the modulation of the Wnt,Hedgehog and Notch signaling pathways.Furthermore,AAV-Rassf2 enhances cochlear supporting cell division and hair cell production in the neomycin injury model.In summary,our results suggest that Rassf2 is a key component in HC regenerative repair,and gene modulation mediated by adeno-associated virus may be a promising gene therapy for hearing repair.
