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...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science (AAAS)
2025-01-01
|
| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0590 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| ISSN: | 2639-5274 |