Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7
Abstract 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 th...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-07-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01421-6 |
| _version_ | 1829485301855158272 |
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| author | Yisheng Gao Jie Liu Jing Huan Fengyuan Che |
| author_facet | Yisheng Gao Jie Liu Jing Huan Fengyuan Che |
| author_sort | Yisheng Gao |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-14T22:43:26Z |
| format | Article |
| id | doaj.art-e51ee153bd574dde89db10e4da468219 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-14T22:43:26Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-e51ee153bd574dde89db10e4da4682192022-12-21T22:44:56ZengBMCCancer Cell International1475-28672020-07-0120111310.1186/s12935-020-01421-6Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7Yisheng Gao0Jie Liu1Jing Huan2Fengyuan Che3Guangzhou University of Chinese MedicineDepartment of Urology, Linyi People’s HospitalGuangzhou University of Chinese MedicineGuangzhou University of Chinese MedicineAbstract 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.http://link.springer.com/article/10.1186/s12935-020-01421-6PCaDTXhsa_circ_0000735miR-7 |
| spellingShingle | Yisheng Gao Jie Liu Jing Huan Fengyuan Che Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7 Cancer Cell International PCa DTX hsa_circ_0000735 miR-7 |
| title | Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7 |
| title_full | Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7 |
| title_fullStr | Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7 |
| title_full_unstemmed | Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7 |
| title_short | Downregulation of circular RNA hsa_circ_0000735 boosts prostate cancer sensitivity to docetaxel via sponging miR-7 |
| title_sort | downregulation of circular rna hsa circ 0000735 boosts prostate cancer sensitivity to docetaxel via sponging mir 7 |
| topic | PCa DTX hsa_circ_0000735 miR-7 |
| url | http://link.springer.com/article/10.1186/s12935-020-01421-6 |
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