Altered Atlas of Exercise-Responsive MicroRNAs Revealing miR-29a-3p Attacks Armored and Cold Tumors and Boosts Anti-B7-H3 Therapy
Jie Mei,
Zhiwen Luo,
Yun Cai,
Renwen Wan,
Zhiwen Qian,
Jiahui Chu,
Yaying Sun,
Yuxin Shi,
Ying Jiang,
Yan Zhang,
Yongmei Yin,
Shiyi Chen
Affiliations
Jie Mei
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Zhiwen Luo
Department of Sports Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China.
Yun Cai
Department of Central Laboratory, Changzhou Jintan First People’s Hospital, Jiangsu University, Changzhou 213200, China.
Renwen Wan
Department of Sports Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China.
Zhiwen Qian
Departments of Gynecology, Wuxi Maternal and Child Health Care Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China.
Jiahui Chu
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Yaying Sun
Department of Sports Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Yuxin Shi
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.
Ying Jiang
Department of Gynecology, The Obstetrics and Gynecology Hospital Affiliated to Jiangnan University, Wuxi 214023, China.
Yan Zhang
Departments of Gynecology, Wuxi Maternal and Child Health Care Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China.
Yongmei Yin
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Shiyi Chen
Department of Sports Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China.
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.
