Altered Atlas of Exercise-Responsive MicroRNAs Revealing miR-29a-3p Attacks Armored and Cold Tumors and Boosts Anti-B7-H3 Therapy
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 mi...
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American Association for the Advancement of Science (AAAS)
2025-01-01
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Online Access: | https://spj.science.org/doi/10.34133/research.0590 |
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author | Jie Mei Zhiwen Luo Yun Cai Renwen Wan Zhiwen Qian Jiahui Chu Yaying Sun Yuxin Shi Ying Jiang Yan Zhang Yongmei Yin Shiyi Chen |
author_facet | Jie Mei Zhiwen Luo Yun Cai Renwen Wan Zhiwen Qian Jiahui Chu Yaying Sun Yuxin Shi Ying Jiang Yan Zhang Yongmei Yin Shiyi Chen |
author_sort | Jie Mei |
collection | DOAJ |
description | 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. |
format | Article |
id | doaj-art-0d043458a134437b9853ea0c1b39eed8 |
institution | Kabale University |
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language | English |
publishDate | 2025-01-01 |
publisher | American Association for the Advancement of Science (AAAS) |
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spelling | doaj-art-0d043458a134437b9853ea0c1b39eed82025-01-22T08:00:31ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0590Altered Atlas of Exercise-Responsive MicroRNAs Revealing miR-29a-3p Attacks Armored and Cold Tumors and Boosts Anti-B7-H3 TherapyJie Mei0Zhiwen Luo1Yun Cai2Renwen Wan3Zhiwen Qian4Jiahui Chu5Yaying Sun6Yuxin Shi7Ying Jiang8Yan Zhang9Yongmei Yin10Shiyi Chen11Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.Department of Sports Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China.Department of Central Laboratory, Changzhou Jintan First People’s Hospital, Jiangsu University, Changzhou 213200, China.Department of Sports Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China.Departments of Gynecology, Wuxi Maternal and Child Health Care Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China.Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.Department of Sports Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.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.Department of Gynecology, The Obstetrics and Gynecology Hospital Affiliated to Jiangnan University, Wuxi 214023, China.Departments of Gynecology, Wuxi Maternal and Child Health Care Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China.Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.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.https://spj.science.org/doi/10.34133/research.0590 |
spellingShingle | Jie Mei Zhiwen Luo Yun Cai Renwen Wan Zhiwen Qian Jiahui Chu Yaying Sun Yuxin Shi Ying Jiang Yan Zhang Yongmei Yin Shiyi Chen Altered Atlas of Exercise-Responsive MicroRNAs Revealing miR-29a-3p Attacks Armored and Cold Tumors and Boosts Anti-B7-H3 Therapy Research |
title | Altered Atlas of Exercise-Responsive MicroRNAs Revealing miR-29a-3p Attacks Armored and Cold Tumors and Boosts Anti-B7-H3 Therapy |
title_full | Altered Atlas of Exercise-Responsive MicroRNAs Revealing miR-29a-3p Attacks Armored and Cold Tumors and Boosts Anti-B7-H3 Therapy |
title_fullStr | Altered Atlas of Exercise-Responsive MicroRNAs Revealing miR-29a-3p Attacks Armored and Cold Tumors and Boosts Anti-B7-H3 Therapy |
title_full_unstemmed | Altered Atlas of Exercise-Responsive MicroRNAs Revealing miR-29a-3p Attacks Armored and Cold Tumors and Boosts Anti-B7-H3 Therapy |
title_short | Altered Atlas of Exercise-Responsive MicroRNAs Revealing miR-29a-3p Attacks Armored and Cold Tumors and Boosts Anti-B7-H3 Therapy |
title_sort | altered atlas of exercise responsive micrornas revealing mir 29a 3p attacks armored and cold tumors and boosts anti b7 h3 therapy |
url | https://spj.science.org/doi/10.34133/research.0590 |
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