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Our previous work has demonstrated that miR-323 enhances tumor angiogenesis in prostate cancer. In the present study, we sought to determine the function of miR-323 in prostate cancer cell growth and response to docetaxel. The effects of miR-323 overexpression on prostate cancer cell proliferation, colony formation, and tumorigenesis were examined. We also investigated the impact of miR-323 knockdown on cell cycle progression and apoptosis. Ectopic expression of miR-323 promoted cell proliferation and colony formation in vitro and xenograft tumor growth in vivo. Depletion of miR-323 arrested PC-3 prostate cancer cells at the G0/G1 phase and caused significant apoptosis, which was coupled with increased expression of p21 and cleavage of caspase-9 and caspase-3 and reduced expression of cyclin D1. Compared to PC-3 parental cells, docetaxel-resistant PC-3-DR cells had 5.6-fold higher levels of miR-323. Overexpression of miR-323 increased the 50% inhibitory concentration (IC50) value for docetaxel in PC-3 cells, while silencing of miR-323 exerted an opposite effect on PC-3-DR cells. Mechanistically, miR-323 repressed the expression of p73 in prostate cancer cells. Knockdown of p73 augmented cell proliferation and colony formation and blunted sensitivity to docetaxel in PC-3 cells. In addition, overexpression of p73 significantly suppressed cell proliferation and induced apoptosis and docetaxel sensitivity in PC-3-DR cells. In conclusion, miR-323 contributes to the aggressive phenotype of prostate cancer cells by targeting p73 and represents a potential therapeutic target for this malignancy.
This article was published in the following journal.
Name: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
High baseline YKL-40 serum levels are associated with drug resistance in several solid tumours. However, their role in predicting docetaxel (DOC) resistance in prostate cancer (PCa) is unknown.
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A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.
A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.
Tissue ablation of the PROSTATE performed by ultrasound from a transducer placed in the RECTUM. The procedure is used to treat prostate cancer (PROSTATIC NEOPLASMS) and benign prostatic hypertrophy (PROSTATIC HYPERPLASIA).
Proteins secreted by the prostate gland. The major secretory proteins from the human prostate gland include PROSTATE-SPECIFIC ANTIGEN, prostate-specific acid phosphatase, prostate-specific membrane antigen, and prostate-specific protein-94.
Tumors or cancer of the PROSTATE.
A microRNA (abbreviated miRNA) is a small non-coding RNA molecule (containing about 22 nucleotides) found in plants, animals, and some viruses. Key findings: miRNA is involved in the normal functioning of eukaryotic cells, so has dysregulation...
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