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

职业与健康 ›› 2023, Vol. 39 ›› Issue (19): 2617-2625.

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

肖楚兰¹, 陈娇娇², 殷子斐³, 李柏²

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

收稿日期:2023-02-24 修回日期:2023-03-27 出版日期:2023-10-01 发布日期:2026-03-26
通信作者: 李柏,主任医师,E-mail：libai9@163.com
作者简介:肖楚兰,男,主治医师,主要从事中西医结合肿瘤康复治疗与研究工作。
基金资助:
海军军医大学第一附属医院长海医院青年启动基金（2019QNB05）

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

XIAO Chulan¹, CHEN Jiaojiao², YIN Zifei³, LI Bai²

1. Traditional Chinese Medicine Department 920th Hospital of Joint Logistic Support Force of PLA,Kunming Yunnan 650000,China;
2. Rehabilitation Department,Changhai Hospital Affiliated to Naval Medical University,Shanghai 200433,China;
3. Military Traditional Chinese Medicine Teaching and Research Office,Department of Traditional Chinese Medicine,Naval Military Medical University,Shanghai 200433,China

Received:2023-02-24 Revised:2023-03-27 Online:2023-10-01 Published:2026-03-26
Contact: LI Bai,Chief physician,E-mail：libai9@163.com

摘要/Abstract

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）mRNA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。

关键词: 有氧运动, 游泳, RNA-seq, 肝细胞癌, IQUB, Wnt/β-catenin信号通路

Abstract: 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 model of HCC,and IQUB may be an upstream regulator of Wnt/β-catenin signaling pathway,and may be a potential target of swimming exercise to inhibit the development of HCC.

Key words: Aerobic exercise, Swimming, RNA-seq, Hepatocellular carcinoma, IQUB, Wnt/β-catenin pathway

中图分类号:

R-332

肖楚兰, 陈娇娇, 殷子斐, 李柏. 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. [J]职业与健康, 2023, 39(19): 2617-2625.

XIAO Chulan, CHEN Jiaojiao, YIN Zifei, LI Bai. Correlation between IQUB and swimming exercise in inhibiting tumor growth in nude mice with hepatocellular carcinomabased on RNA-seq. [J]OCCUPATION AND HEALTH, 2023, 39(19): 2617-2625.

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