miR-103a-2-5p/miR-30c-1-3p inhibits the progression of prostate cancer resistance to androgen ablation therapy via targeting androgen receptor variant 7
| Autor: | Gan Yao, Keqin Zhou, Wenjie Chen |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Untranslated region Male medicine.drug_class Cell Survival Biochemistry 03 medical and health sciences Prostate cancer chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor microRNA medicine Enzalutamide Humans Molecular Biology 3' Untranslated Regions Cell Proliferation Messenger RNA Base Sequence Cell growth business.industry Prostatic Neoplasms Cell Biology Androgen medicine.disease Androgen receptor Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology chemistry Receptors Androgen 030220 oncology & carcinogenesis Cancer research Androgens Disease Progression business Protein Binding |
| Zdroj: | Journal of cellular biochemistry. 120(8) |
| ISSN: | 1097-4644 |
| Popis: | Androgens and androgen receptors are vital factors involved in prostate cancer progression, and androgen ablation therapies are commonly used to treat advanced prostate cancer. However, the acquisition of androgen ablation therapy resistance remains a challenge. Recently, androgen receptor splicing variants lacking the ligand-binding domain have been reported to play a critical role in the acquisition of androgen ablation therapy resistance. In the present study, we revealed that the messenger RNA expression and the protein levels of an androgen receptor variant 7 (AR-V7) were higher in prostate cancer tissue samples and in the AR-positive prostate cancer cell line, VCaP. In contrast, microRNA (miR)-30c-1-3p/miR-103a-2-5p expression was significantly downregulated in tumor tissues and cells. miR-30c-1-3p/miR-103a-2-5p overexpression could inhibit AR-V7 expression, suppress VCaP cell growth, and inhibit AR-V7 downstream factor expression by directly targeting the 3'-untranslated region of AR-V7. Under enzalutamide (Enza) treatment, the effects of AR-V7 overexpression were the opposite of those of miR-103a-2-5p/miR-30c-1-3p overexpression; more importantly, the effects of miR-103a-2-5p/miR-30c-1-3p overexpression could be significantly reversed by AR-V7 overexpression under Enza. In summary, we demonstrated a novel mechanism of the miR-30c-1-3p/miR-103a-2-5p/AR-V7 axis modulating the cell proliferation of AR-positive prostate cancer cells via AR downstream targets. The clinical application of miR-30c-1-3p/miR-103a-2-5p needs further in vivo validation. |
| Databáze: | OpenAIRE |
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