MiR-7 mediates mitochondrial impairment to trigger apoptosis and necroptosis in Rhabdomyosarcoma
Lin Yang1, Delin Kong1, Mei He1
1Key Laboratory of Saline-alkali Vegetation Ecology Restoration, College of Life Science, Northeast Forestry University, Harbin, China.
Background:
Rhabdomyosarcoma (RMS) is a pediatric cancer with rhabdomyoblastic phenotype and mitochondria act as pivotal regulators of its growth and progression. While miR-7-5p (miR-7) is reported to have a tumor-suppressive role, little is yet known about its antitumor activity in RMS.
Methods:
The effects of miR-7 on RMS were analyzed both in vitro and in vivo. Cell death modalities induced by miR-7 were identified. Influence on mitochondria was evaluated through RNA sequencing data, morphological observation and mitochondrial functional assays, including outer membrane permeability, bioenergetics and redox balance. Dual-luciferase assay and phenotype validation after transient gene silencing were performed to identify miR-7 targets in RMS.
Results:
MiR-7 executed anti-tumor effect in RMS beyond proliferation inhibition. Morphologic features and molecular characteristics with apoptosis and necroptosis were found in miR-7-transfected RMS cells. Chemical inhibitors of apoptosis and necroptosis were able to prevent miR-7-induced cell death. Further, we identified that mitochondrial impairment mainly contributed to these phenomena and mitochondrial proteins SLC25A37 and TIMM50 were crucial targets for miR-7 to induce cell death in RMS.
Conclusion:
Our results extended the mechanism of miR-7 antitumor role in rhabdomyosarcoma cancer, and provided potential implications for its therapy.
Insights
MicroRNA-7 (miR-7) exhibits anti-tumor effects in rhabdomyosarcoma (RMS) by inducing apoptosis and necroptosis. It targets mitochondrial proteins SLC25A37 and TIMM50, offering potential therapeutic strategies for this pediatric cancer.
Area of Science:
- Molecular Biology
- Oncology
- Mitochondrial Biology
Background:
- Rhabdomyosarcoma (RMS) is a pediatric cancer driven by mitochondrial function.
- MicroRNA-7 (miR-7) is a known tumor suppressor, but its role in RMS is largely unexplored.
- Mitochondria are critical regulators of RMS growth and progression.
Purpose of the Study:
- To investigate the antitumor activity of miR-7 in rhabdomyosarcoma (RMS).
- To elucidate the mechanisms by which miR-7 exerts its effects on RMS cells.
- To identify potential therapeutic targets for miR-7-based treatments in RMS.
Main Methods:
- In vitro and in vivo analysis of miR-7 effects on RMS.
- Assessment of cell death modalities (apoptosis, necroptosis) induced by miR-7.
- Mitochondrial function assays and RNA sequencing to evaluate mitochondrial impact.
- Identification of miR-7 targets using dual-luciferase assays and gene silencing.
Main Results:
- MiR-7 demonstrated anti-tumor effects in RMS, extending beyond proliferation inhibition.
- miR-7 induced apoptosis and necroptosis in RMS cells, which could be blocked by chemical inhibitors.
- Mitochondrial impairment was identified as a key mechanism, with SLC25A37 and TIMM50 as crucial miR-7 targets.
Conclusions:
- MiR-7 plays a significant antitumor role in rhabdomyosarcoma.
- The mechanism involves targeting mitochondrial proteins SLC25A37 and TIMM50, leading to cell death.
- These findings suggest potential therapeutic implications for miR-7 in RMS treatment.
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