Prostate cancer small extracellular vesicles participate in androgen-independent transformation of prostate cancer by transferring let-7a-5p

• Published in: Heliyon 2022-12, Vol.8 (12), p.e12114-e12114, Article e12114
• Main Authors: Lei, Lin, Yu, Lijuan, Fan, Weixiao, Hao, Xiaoke
• Format: Article
• Language: English
• Subjects: Androgen receptor signaling pathway; Androgen-dependent PCa; Androgen-independent PCa; Castration-resistant PCa; Let-7a-5p; PI3K/Akt signaling pathway
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2022.e12114

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. 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. 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-7a-5p 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. 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. Prostate cancer sEVs participate in androgen-independent transformation of prostate cancer by transferring let-7a-5p. [Display omitted] Androgen-independent PCa; androgen-dependent PCa; castration-resistant PCa; let-7a-5p, androgen receptor signaling pathway; PI3K/Akt signaling pathway.