Osteoblast-derived exosomal miR-140-3p targets ACER2 and increases the progression of prostate cancer via the AKT/mTOR pathway-mediated inhibition of autophagy
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View abstract on PubMed
Summary
This summary is machine-generated.Exosomal miR-140-3p from osteoblasts promotes advanced prostate cancer (aPCa) bone metastasis by inhibiting autophagy via the AKT/mTOR pathway. This microRNA is a potential biomarker for aPCa bone metastasis.
Area Of Science
- Oncology
- Molecular Biology
- Cell Biology
Background
- Advanced prostate cancer (aPCa) frequently metastasizes to bone (BM), but the underlying mechanisms are not fully understood.
- MicroRNAs (miRNAs) are implicated in cancer progression, and exosomal miRNAs are crucial for intercellular communication.
Purpose Of The Study
- To investigate the role of exosomal miR-140-3p in prostate cancer (PCa) progression and bone metastasis.
Main Methods
- Analysis of serum exosomal miR-140-3p levels in PCa patients with and without BM.
- In vitro studies using PCa cell lines to assess the effects of miR-140-3p on proliferation, invasion, and migration.
- Animal models and analysis of PCa tissues to evaluate tumorigenesis and metastasis.
- Western blot analysis to assess protein expression related to the AKT/mTOR pathway and autophagy.
Main Results
- Patients with PCa and BM showed significantly higher serum exosomal miR-140-3p levels compared to those without BM.
- Exosomal miR-140-3p overexpression correlated with serum PSA levels and Gleason grade.
- In vitro, osteoblast-derived exosomal miR-140-3p targeted ACER2, activated the AKT/mTOR pathway, inhibited autophagy, and promoted PCa cell proliferation, invasion, and migration.
- miR-140-3p significantly increased PCa tumorigenesis and metastasis in vivo.
- Bone metastatic PCa tissues exhibited elevated levels of miR-140-3p and markers of AKT/mTOR pathway activation, with decreased levels of ACER2 and LC3 II.
Conclusions
- Osteoblast-derived exosomal miR-140-3p plays a critical role in promoting PCa progression and bone metastasis.
- The mechanism involves targeting ACER2, activating the AKT/mTOR pathway, and inhibiting autophagy.
- Exosomal miR-140-3p is a potential diagnostic and prognostic biomarker for PCa bone metastasis.
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