Prostate cancer small extracellular vesicles participate in androgen-independent transformation of prostate cancer by transferring let-7a-5p
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 unclea...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022034028 |
| _version_ | 1828071316030226432 |
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| author | Lin Lei Lijuan Yu Weixiao Fan Xiaoke Hao |
| author_facet | Lin Lei Lijuan Yu Weixiao Fan Xiaoke Hao |
| author_sort | Lin Lei |
| collection | DOAJ |
| description | 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-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. 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. |
| first_indexed | 2024-04-11T00:52:36Z |
| format | Article |
| id | doaj.art-c1d6196bb4764b4abf98e03454312ec4 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-11T00:52:36Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-c1d6196bb4764b4abf98e03454312ec42023-01-05T08:38:44ZengElsevierHeliyon2405-84402022-12-01812e12114Prostate cancer small extracellular vesicles participate in androgen-independent transformation of prostate cancer by transferring let-7a-5pLin Lei0Lijuan Yu1Weixiao Fan2Xiaoke Hao3Institute of Laboratory Medicine Center of Chinese People’s Liberation Army (PLA), Xijing Hospital, Fourth Military Medical University (Air Force Medical University), China; Department of Clinical Laboratory Medicine, Xi’an Hospital of Traditional Chinese Medicine, ChinaInstitute of Laboratory Medicine Center of Chinese People’s Liberation Army (PLA), Xijing Hospital, Fourth Military Medical University (Air Force Medical University), China; Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, China; Krefting Research Centre, Institute of Medicine, University of Gothenburg, Sweden; Corresponding author.Institute of Laboratory Medicine Center of Chinese People’s Liberation Army (PLA), Xijing Hospital, Fourth Military Medical University (Air Force Medical University), China; College of Medicine, Northwest University, ChinaInstitute of Laboratory Medicine Center of Chinese People’s Liberation Army (PLA), Xijing Hospital, Fourth Military Medical University (Air Force Medical University), China; College of Medicine, Northwest University, China; Corresponding author.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-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. 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.http://www.sciencedirect.com/science/article/pii/S2405844022034028Androgen-independent PCaAndrogen-dependent PCaCastration-resistant PCaLet-7a-5pAndrogen receptor signaling pathwayPI3K/Akt signaling pathway |
| spellingShingle | Lin Lei Lijuan Yu Weixiao Fan Xiaoke Hao Prostate cancer small extracellular vesicles participate in androgen-independent transformation of prostate cancer by transferring let-7a-5p Heliyon Androgen-independent PCa Androgen-dependent PCa Castration-resistant PCa Let-7a-5p Androgen receptor signaling pathway PI3K/Akt signaling pathway |
| title | Prostate cancer small extracellular vesicles participate in androgen-independent transformation of prostate cancer by transferring let-7a-5p |
| title_full | Prostate cancer small extracellular vesicles participate in androgen-independent transformation of prostate cancer by transferring let-7a-5p |
| title_fullStr | Prostate cancer small extracellular vesicles participate in androgen-independent transformation of prostate cancer by transferring let-7a-5p |
| title_full_unstemmed | Prostate cancer small extracellular vesicles participate in androgen-independent transformation of prostate cancer by transferring let-7a-5p |
| title_short | Prostate cancer small extracellular vesicles participate in androgen-independent transformation of prostate cancer by transferring let-7a-5p |
| title_sort | prostate cancer small extracellular vesicles participate in androgen independent transformation of prostate cancer by transferring let 7a 5p |
| topic | Androgen-independent PCa Androgen-dependent PCa Castration-resistant PCa Let-7a-5p Androgen receptor signaling pathway PI3K/Akt signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022034028 |
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