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运动增强的 THSD7B 在泛癌中表现出积极的预后意义和肿瘤抑制功能。

Exercise-augmented THSD7B exhibited a positive prognostic implication and tumor-suppressed functionality in pan-cancer.

机构信息

Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Department of Orthopaedics, Nantong Tongzhou Hospital of Traditional Chinese Medicine, Tongzhou, Jiangsu, China.

出版信息

Front Immunol. 2024 Aug 5;15:1440226. doi: 10.3389/fimmu.2024.1440226. eCollection 2024.

Abstract

BACKGROUND

Breast cancer, one of the most prevalent malignancies among women worldwide, has rising incidence rates. Physical activity, particularly exercise, has emerged as a significant modifier of cancer prognosis, influencing both tumor biology and patient outcomes.

METHODS

In this study, we utilized a murine breast cancer model, dividing mice into a control group and an exercise group; the latter underwent 21 days of voluntary running. We conducted RNA sequencing, bioinformatics analysis, pan-cancer analysis, and cellular experiments to investigate the underlying mechanisms influenced by exercise.

RESULTS

Exercise led to a significant reduction in tumor size and weight. Post-exercise mRNA sequencing indicated a notable upregulation of THSD7B in the exercised mice, with significant alterations observed in pathways such as MicroRNAs in cancers and the Calcium signaling pathway. In a broader cancer context, THSD7B showed considerable expression variability, being significantly downregulated in several cancers, correlating with positive prognostic outcomes in PRAD, LAML, KIRC, and GBM and highlighting its potential role as a prognostic marker and therapeutic target. THSD7B expression was also negatively associated with processes of breast cancer cell proliferation, migration, and invasion.

CONCLUSION

This study underscores the dual role of exercise in modulating gene expression relevant to tumor growth and highlights the potential of THSD7B as a therapeutic target in cancer. Future research should further explore the specific mechanisms by which exercise and THSD7B influence cancer progression and develop immunotherapy-enhanced strategies to change patient outcomes in clinical settings.

摘要

背景

乳腺癌是全球女性最常见的恶性肿瘤之一,其发病率呈上升趋势。身体活动,尤其是运动,已成为癌症预后的重要调节剂,影响肿瘤生物学和患者结局。

方法

在本研究中,我们使用了一种小鼠乳腺癌模型,将小鼠分为对照组和运动组;后者进行了 21 天的自愿跑步。我们进行了 RNA 测序、生物信息学分析、泛癌分析和细胞实验,以研究运动影响的潜在机制。

结果

运动导致肿瘤大小和重量显著减小。运动后的 mRNA 测序表明,运动小鼠中 THSD7B 的表达显著上调,在 MicroRNAs in cancers 和 Calcium signaling pathway 等途径中观察到显著变化。在更广泛的癌症背景下,THSD7B 表现出相当大的表达变异性,在几种癌症中显著下调,与 PRAD、LAML、KIRC 和 GBM 中的阳性预后结果相关,突出了其作为预后标志物和治疗靶点的潜力。THSD7B 的表达与乳腺癌细胞增殖、迁移和侵袭过程呈负相关。

结论

本研究强调了运动在调节与肿瘤生长相关的基因表达方面的双重作用,并突出了 THSD7B 作为癌症治疗靶点的潜力。未来的研究应进一步探讨运动和 THSD7B 影响癌症进展的具体机制,并开发免疫治疗增强策略,以改变临床环境中的患者结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebb9/11330788/232ef91986be/fimmu-15-1440226-g001.jpg

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