Journal
HELIYON
Volume 8, Issue 12, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.heliyon.2022.e12114
Keywords
Androgen-independent PCa; Androgen-dependent PCa; Castration-resistant PCa; Let-7a-5p; Androgen receptor signaling pathway; PI3K /Akt signaling pathway
Categories
Funding
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- National Natural Science Founda-tion of China
- [82203711]
- [2021M701631]
- [81872347]
Ask authors/readers for more resources
This study reveals the significant role of small extracellular vesicles (sEVs) in the androgen-independent transformation of prostate cancer. By transferring the key sEVs molecule Let-7a-5p and activating the androgen receptor (AR) and PI3K/Akt signaling pathways, sEVs regulate the process. This finding provides new perspectives for targeted treatment approaches for AIPC patients.
Objectives: Androgen deprivation therapy (ADT) is a standard treatment for advanced prostate cancer (PCa). However, after 2-3 years ADT treatment, prostate cancer inevitably transits from androgen-dependent PCa (ADPC) to androgen-independent PCa (AIPC), which has a poor prognosis owing to its unclear mechanism and lack of effective therapeutic targets. Small extracellular vesicles (sEVs) play a vital role in the development of cancer. However, the role of PCa sEVs in the transformation of AIPC remains poorly understood. Materials and methods: Two different cell models were employed and compared. sEVs from ADPC cells (LNCaP) and AIPC cells (LNCaP-AI + F cells) were isolated and characterized. After co-culture of LNCaP-AI + F sEVs with LNCaP cells and of LNCaP sEVs with LNCaP-AI + F cells, androgen-independent transformation was determined respectively. Mechanically, small RNA sequencing was performed. Androgen-independent transformation was examined by the upregulation and downregulation of miRNA and downstream pathways were analyzed. Results: LNCaP-AI + F sEVs promoted the androgen-independent transformation of LNCaP cells. Interestingly, LNCaP sEVs exhibited a capacity to reverse the process.Let-7a-5p transfer was demonstrated. Furthermore, let-7a5p overexpression promotes the androgen-independent transformation and let-7a-5p down-regulation reverses the process. Androgen receptor (AR) and PI3K/Akt pathways were identified and demonstrated by both let-7a-5p regulation and PCa sEVs coculture. Conclusions: PCa sEVs are intimately involved in the regulation of androgen-independent transformation of prostate cancer by transferring the key sEVs molecular let-7a-5p and then activating the AR and PI3K/Akt signaling pathways. Our results provide new perspectives for the development of sEVs and sEVs molecular targeted treatment approaches for AIPC patients.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available