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Sheetz T, Mills J, Tessari A, et al. NCL Inhibition Exerts Antineoplastic Effects against Prostate Cancer Cells by Modulating Oncogenic MicroRNAs. Cancers (Basel). 2020;12(7)doi: 10.3390/cancers12071861.
Sheetz, T., Mills, J., Tessari, A., Pawlikowski, M., Braddom, A. E., Posid, T., Zynger, D. L., James, C., Embrione, V., Parbhoo, K., Foray, C., Coppola, V., Croce, C. M., & Palmieri, D. (2020). NCL Inhibition Exerts Antineoplastic Effects against Prostate Cancer Cells by Modulating Oncogenic MicroRNAs. Cancers, 12(7), . https://doi.org/10.3390/cancers12071861
Sheetz, Tyler, et al. "NCL Inhibition Exerts Antineoplastic Effects against Prostate Cancer Cells by Modulating Oncogenic MicroRNAs." Cancers vol. 12,7 (2020). doi: https://doi.org/10.3390/cancers12071861
Sheetz T, Mills J, Tessari A, Pawlikowski M, Braddom AE, Posid T, Zynger DL, James C, Embrione V, Parbhoo K, Foray C, Coppola V, Croce CM, Palmieri D. NCL Inhibition Exerts Antineoplastic Effects against Prostate Cancer Cells by Modulating Oncogenic MicroRNAs. Cancers (Basel). 2020 Jul 10;12(7). doi: 10.3390/cancers12071861. PMID: 32664322; PMCID: PMC7408652.
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Cancers (Basel). 2020 Jul 10;12(7). doi: 10.3390/cancers12071861.

NCL Inhibition Exerts Antineoplastic Effects against Prostate Cancer Cells by Modulating Oncogenic MicroRNAs.

Cancers

Tyler Sheetz, Joseph Mills, Anna Tessari, Megan Pawlikowski, Ashley E Braddom, Tasha Posid, Debra L Zynger, Cindy James, Valerio Embrione, Kareesma Parbhoo, Claudia Foray, Vincenzo Coppola, Carlo M Croce, Dario Palmieri

Affiliations

  1. Department of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
  2. Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
  3. Department of Urology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
  4. Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
  5. Mass Spectroscopy and Proteomics Facility, The Ohio State University, Columbus, OH 43210, USA.

PMID: 32664322 PMCID: PMC7408652 DOI: 10.3390/cancers12071861

Abstract

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and second most common cause of cancer-related deaths in the United States. Androgen deprivation therapy (ADT) is only temporarily effective for advanced-stage PCa, as the disease inevitably progresses to castration-resistant prostate cancer (CRPC). The protein nucleolin (NCL) is overexpressed in several types of human tumors where it is also mislocalized to the cell surface. We previously reported the identification of a single-chain fragment variable (scFv) immuno-agent that is able to bind NCL on the surface of breast cancer cells and inhibit proliferation both in vitro and in vivo. In the present study, we evaluated whether NCL could be a valid therapeutic target for PCa, utilizing DU145, PC3 (CRPC), and LNCaP (androgen-sensitive) cell lines. First, we interrogated the publicly available databases and noted that higher NCL mRNA levels are associated with higher Gleason Scores as well as with recurrent and metastatic tumors. Then, using our anti-NCL scFv, we demonstrated that NCL is expressed on the surface of all three tested cell lines and that NCL inhibition results in reduced proliferation and migration. We also measured the inhibitory effect of NCL targeting on the biogenesis of oncogenic microRNAs such as miR-21, -221 and -222, which was cell context dependent. Taken together, our data provide evidence that NCL targeting inhibits the key hallmarks of malignancy in PCa cells and may provide a novel therapeutic option for patients with advanced-stage PCa.

Keywords: castration-resistant prostate cancer; microRNAs; nucleolin; prostate cancer

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