Cargando…
Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7
BACKGROUND: One of the main reasons for the failure of prostate cancer (PCa) treatment is the generation of chemoresistance. Circular RNA hsa_circ_0000735 (hsa_circ_0000735) is connected with the progression of cancer. Nevertheless, the role and regulatory mechanism of hsa_circ_0000735 in the resist...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376840/ https://www.ncbi.nlm.nih.gov/pubmed/32714093 http://dx.doi.org/10.1186/s12935-020-01421-6 |
Sumario: | BACKGROUND: One of the main reasons for the failure of prostate cancer (PCa) treatment is the generation of chemoresistance. Circular RNA hsa_circ_0000735 (hsa_circ_0000735) is connected with the progression of cancer. Nevertheless, the role and regulatory mechanism of hsa_circ_0000735 in the resistance of PCa to docetaxel (DTX) are unclear. METHODS: Expression levels of hsa_circ_0000735 and miR-7-5p (miR-7) in tissue samples and cells were examined via quantitative real-time polymerase chain reaction (qRT-PCR). The DTX sensitivity, viability, colony formation, cell cycle progression, and apoptosis of DTX-resistant PCa cells were determined via Cell Counting Kit-8 (CCK-8), cell colony formation, or flow cytometry assays. The levels of multidrug resistance protein 1 (MDR1) protein, cyclinD1, and B cell lymphoma 2 (bcl-2) were detected by western blotting. The interaction between hsa_circ_0000735 and miR-7 was verified via dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. The role of hsa_circ_0000735 in vivo was validated through tumor formation experiments. RESULTS: Hsa_circ_0000735 was upregulated and miR-7 was downregulated in DTX-resistant PCa tissues and cells. High hsa_circ_0000735 expression had a shorter overall survival. Both hsa_circ_0000735 knockdown and miR-7 mimic boosted DTX sensitivity, constrained viability, colony formation, cell cycle progression, and fostered apoptosis of DTX-resistant PCa cells. Also, hsa_circ_0000735 silencing elevated DTX sensitivity and repressed tumor growth in PCa in vivo. Mechanistically, hsa_circ_0000735 served as a sponge for miR-7. MiR-7 inhibition overturned hsa_circ_0000735 silencing-mediated impacts on DTX sensitivity and the malignant behaviors of DTX-resistant PCa cells. CONCLUSION: Hsa_circ_0000735 downregulation boosted PCa sensitivity to DTX and reduced tumor growth via sponging miR-7, providing a promising prognostic biomarker and therapeutic target for PCa. |
---|