microRNA-323 upregulation promotes prostate cancer growth and docetaxel resistance by repressing p73.

08:00 EDT 29th October 2017 | BioPortfolio

Summary of "microRNA-323 upregulation promotes prostate cancer growth and docetaxel resistance by repressing p73."

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.


Journal Details

This article was published in the following journal.

Name: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
ISSN: 1950-6007
Pages: 528-534


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Medical and Biotech [MESH] Definitions

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.

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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.

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