Altered Atlas of Exercise-Responsive MicroRNAs Revealing miR-29a-3p Attacks Armored and Cold Tumors and Boosts Anti-B7-H3 Therapy

  • Research (Wash D C). 2025 Jan 22:8:0590. doi: 10.34133/research.0590.
Jie Mei  1  2 ,  Zhiwen Luo  3 ,  Yun Cai  4 ,  Renwen Wan  3 ,  Zhiwen Qian  5 ,  Jiahui Chu  1  2 ,  Yaying Sun  6 ,  Yuxin Shi  7 ,  Ying Jiang  8 ,  Yan Zhang  5  8 ,  Yongmei Yin  1  9  10 ,  Shiyi Chen  3
Affiliations
  • 1. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • 2. The First Clinical Medicine College, Nanjing Medical University, Nanjing 211166, China.
  • 3. Department of Sports Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China.
  • 4. Department of Central Laboratory, Changzhou Jintan First People's Hospital, Jiangsu University, Changzhou 213200, China.
  • 5. Departments of Gynecology, Wuxi Maternal and Child Health Care Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China.
  • 6. Department of Sports Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
  • 7. Department of Oncology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Nanjing 211166, China.
  • 8. Department of Gynecology, The Obstetrics and Gynecology Hospital Affiliated to Jiangnan University, Wuxi 214023, China.
  • 9. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing 211166, China.
  • 10. Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China.
PMID: 39845707 DOI: 10.34133/research.0590
Abstract

Increasing evidence has shown that physical exercise remarkably inhibits oncogenesis and progression of numerous cancers and exercise-responsive MicroRNAs (miRNAs) exert a marked role in exercise-mediated tumor suppression. In this research, expression and prognostic values of exercise-responsive miRNAs were examined in breast Cancer (BRCA) and further pan-cancer types. In addition, multiple independent public and in-house cohorts, in vitro assays involving multiple, macrophages, fibroblasts, and tumor cells, and in vivo models were utilized to uncover the tumor-suppressive roles of miR-29a-3p in cancers. Here, we reported that miR-29a-3p was the exercise-responsive miRNA, which was lowly expressed in tumor tissues and associated with unfavorable prognosis in BRCA. Mechanistically, miR-29a-3p targeted macrophages, fibroblasts, and tumor cells to down-regulate B7 homolog 3 (B7-H3) expression. Single-cell RNA Sequencing (scRNA-seq) and cytometry by time-of-flight (CyTOF) demonstrated that miR-29a-3p attacked the armored and cold tumors, thereby shaping an immuno-hot tumor microenvironment (TME). Translationally, liposomes were developed and loaded with miR-29a-3p (lipo@miR-29a-3p), and lipo@miR-29a-3p exhibited promising antitumor effects in a mouse model with great biocompatibility. In conclusion, we uncovered that miR-29a-3p is a critical exercise-responsive miRNA, which attacked armored and cold tumors by inhibiting B7-H3 expression. Thus, miR-29a-3p restoration could be an alternative strategy for antitumor therapy.

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