恒河猴增龄过程中miR-16-5p及靶基因在外周血白细胞中的表达变化  

Expression of miR-16-5p and its target mRNA in peripheral blood leukocytes during aging procese of rhesus mulatta

作　　者：胡婧雯[1] 李艳艳[1] 刘伟[2] 焦丽 杨晶 杨云 和占龙[1] 彭小忠[1,2] 鲁帅尧[1] HU Jing-wen;LI Yan-yan;LIU Wei;JIAO Li;YANG Jing;YANG Yun;HE Zhan-long;PENG Xiao-zhong;LU Shuai-yao(Institute of Medical Biology,CAMS & PUMC,Kunming 650107;Department of Molecular Biology and Biochemistry,State Key Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,CAMS & PUMC,Beijing 100005,China)

机构地区：[1]中国医学科学院北京协和医学院医学生物学研究所,云南昆明650107 [2]中国医学科学院北京协和医学院基础医学研究所医学分子生物学国家重点实验室生物化学与分子生物学系,北京100005

出　　处：《基础医学与临床》2019年第7期995-1000,共6页Basic and Clinical Medicine

基　　金：中国医学科学院医学与健康科技创新工程重大协同创新项目(2018-I2M-1-002)

摘　　要：目的明确衰老相关microRNA与恒河猴增龄的相关性。方法将猴群参照人类增龄划分为幼年、成年、老年和长寿,提取外周血白细胞的总RNA;用real-time PCR检测外周血白细胞中的microRNA及VEGFA、GHR、TBP、INSR、CLOCK、IKBKB、PIK3R1、LRP2、SSTR3、IGF1R、BCL2、PPM1D、IRS1、MAPK8、ADCY5、APP、NFE2L1、BDNF和PEX5的表达;利用microRNA靶基因预测网站miRwalk、TargetSan、miRecords、miRDB预测miR-16-5p的靶基因,并与人类衰老基因库(http://genomics.senescence.info/)对接。结果在增龄过程中,恒河猴外周血白细胞中miR-16-5p的表达量随年龄增长而增加(P<0.001);多个网站对miR-16-5p靶基因预测得到539个潜在的靶基因,与人类衰老基因组库对接后有19个基因重合;有10个基因的mRNA在恒河猴增龄过程中存在差异表达,其中,IKBKB、PIK3R1、IRS1的表达随着年龄的增加逐渐下降。结论在自然衰老恒河猴的外周血白细胞中,miR-16-5p及其靶基因IKBKB、PIK3R1、IRS1能作为外周血衰老候选标志物。Objective To clarify the correlation between microRNA and aging in rhesus mulatta.Methods The monkeys were divided into four different age groups as the infant,adult,old and longevity.Real-time PCR was used to detect the expression of microRNA and VEGFA,GHR,TBP,INSR,CLOCK,IKBKB,PIK3R1,LRP2,SSTR3,IGF1R,BCL2,PPM1D,IRS1,MAPK8,ADCY5,APP,NFE2L1,BDNF,PEX5 in peripheral blood leukocytes.Using microRNA target genes forecast website miRwalk,TargetSan,miRecords,miRDB to predicte miR-16-5p target genes.Next the predicted results were docked with Human Ageing Genomic Resources(http://genomics.senescence.info/).Results The expression of miR-16-5p in peripheral blood leukocytes of aging rhesus macaques tended to increase with age(P<0.001).The predicted target genes of miR-16-5p were 539,and 19 of these were overlapped with Human Ageing Genomic Resources.It was showed that ten mRNA of 19 genes were detected and their expressions were different in the aging process of rhesus monkeys.The expressions of IKBKB,PIK3R1 and IRS1 were gradually decreased with aging as compared with the infant group.Conclusions The miR-16-5p can be used as a biomarker of peripheral blood leukocytes in rhesus monkeys.And IKBKB,PIK3R1,IRS1 may be the target genes of miR-16-5p in the aging process of rhesus monkeys.

关 键 词：衰老 恒河猴 miR-16-5p 标志物 

分 类 号：Q74[生物学—分子生物学]