基于RNA-Seq探讨IQUB与游泳运动抑制肝癌裸鼠肿瘤生长的相关性  

Correlation between IQUB and swimming exercise in inhibiting tumor growth in nude mice with hepatocellular carcinomabased on RNA-seq

作　　者：肖楚兰 陈娇娇 殷子斐 李柏 XIAO Chulan;CHEN Jiaojiao;YIN Zifei;LI Bai(Traditional Chinese Medicine Department,920th Hospital of Joint Logistic Support Force of PLA,Kunming Yunnan,650000,China;Rehabilitation Department,Changhai Hospital Affiliated to Naval Medical University,Shanghai,200433,China;Military Traditional Chinese Medicine Teaching and Research Office,Department of Traditional Chinese Medicine,Naval Military Medical University,Shanghai,200433,China)

机构地区：[1]解放军联勤保障部队第920医院中医科,云南昆明650000 [2]海军军医大学附属长海医院康复科,上海200433 [3]海军军医大学中医系军事中医学教研室,上海200433

出　　处：《职业与健康》2023年第19期2617-2625,共9页Occupation and Health

基　　金：海军军医大学第一附属医院长海医院青年启动基金(2019QNB05)。

摘　　要：目的基于转录组测序技术(RNA-Sequence,RNA-seq)探讨游泳运动对肝癌裸鼠肿瘤生长发挥抑制作用的分子机制。方法将10只4周龄Balb/C雄性裸鼠随机分为运动组、对照组。运动组裸鼠游泳适应1周后进行皮下瘤接种,之后进行为期4周的游泳训练(0体质量负荷,30 min/d,5 d/周,连续4周)。游泳训练4周后处死裸鼠收集血清并测量瘤重,使用RNA-seq分析相关干预机制;以实时逆转录聚合酶链反应测定(real-time reverse transcription polymerase chain reaction assay,RT-qPCR)验证游泳运动对裸鼠肝癌组织IQ基序和所含泛素域(IQ motif and ubiquitin domain containing,IQUB)m RNA表达的影响;以裸鼠血清对肝癌细胞系SMMC-7721进行干预探究裸鼠血清对肝癌细胞Wnt/β-catenin信号通路以及IQUB mRNA表达的影响。结果运动组瘤重平均值为(0.136±0.020)g,较对照组的(0.290±0.099)g显著下降(P<0.05)。RNA-Seq结果显示,差异基因IQUB可能在游泳运动的抗肝癌作用中发挥重要作用,且与Wnt/β-catenin信号通路密切相关。运动组裸鼠瘤组织相较于对照组的IQUB相对表达量为0.23±0.05(P<0.05);运动血清干预组肝癌细胞相较于对照组的IQUB mRNA相对表达量为0.22±0.03(P<0.05)。运动组裸鼠血清能够抑制LiCl对肝癌细胞Wnt/β-catenin信号通路的激活,在裸鼠血清与LiCl的共干预下,肝癌细胞的IQUB表达趋势与Wnt/β-catenin信号通路的蛋白表达情况一致。结论游泳运动可以抑制肝癌模型裸鼠的肿瘤生长,IQUB可能是Wnt/β-catenin信号通路的上游调控因子,并有可能是游泳运动抑制肝癌发生发展的潜在靶点。Objective To investigate the molecular mechanism of swimming exercise in inhibiting tumor growth in nude mice with hepatocellular carcinoma(HCC)based onRNA-Sequence(RNA-seq).Methods Ten 4-week-old BALB/c male nude mice were randomly divided into swimming group and control group.The nude mice in the swimming group received subcutaneous tumor inoculation for 1 week after swimming acclimation,and then received swimming training for 4 weeks(0 weight bearing,30 min/d,5 days/week,consecutive four weeks).After 4 weeks of swimming training,nude mice were sacrificed.Serum was collected and tumor tissues were measured.RNA-seq was used to analyze the related intervention mechanism.The real-time reverse transcription polymerase chain reaction assay(RT-qPCR)was used to verify the effect of swimming exercise on IQ motif and ubiquitin domain containing(IQUB)mRNA expression in HCC tissues of nude mice.Based on hepatocellular carcinoma cell line SMMC-7721,the effects of nude mouse serum on proliferation,Wnt/β-catenin signaling pathway and IQUB mRNA expression of SMMC-7721.Results The average tumor weight of exercise group was(0.136±0.020)g,which was significantly decreased compared with control group[(0.290±0.099)g](P<0.05).The results of RNA-Seq showed that the differential gene IQUB may play an important role in the anti-HCC effect of swimming,and it is closely related to the Wnt/β-catenin signaling pathway.Compared with the control group,the relative expression level of IQUB in the exercise group was 0.23±0.05(P<0.05).Compared with the control group,the relative expression level of IQUB mRNA in exercise serum intervention group was 0.22±0.03(P<0.05).The serum of nude mice in exercise group could inhibit the activation of Wnt/β-catenin signaling pathway of HCC cells by LiCl.The expression trend of IQUB in HCC cells was consistent with the protein expression of Wnt/β-catenin signaling pathway under the co-intervention of nude mouse serum and LiCl.Conclusion The swimming exercise can inhibit tumor growth in nude mice mode

关 键 词：有氧运动 游泳 RNA-SEQ 肝细胞癌 IQUB WNT/Β-CATENIN信号通路 

分 类 号：R-332[医药卫生]