UMMS Affiliation

Department of Cell and Developmental Biology

Date

10-25-2016

Document Type

Article

Disciplines

Cancer Biology

Abstract

While decades of research have identified molecular pathways inducing and promoting stages of prostate cancer malignancy, studies addressing dynamic changes of cancer-related regulatory factors in a prostate tumor progression model are limited. Using the TRAMP mouse model of human prostate cancer, we address mechanisms of deregulation for the cancer-associated transcription factors, Runx1 and Runx2 by identifying microRNAs with reciprocal expression changes at six time points during 33 weeks of tumorigenesis. We molecularly define transition stages from PIN lesions to hyperplasia/neoplasia and progression to adenocarcinoma by temporal changes in expression of human prostate cancer markers, including the androgen receptor and tumor suppressors, Nkx3.1 and PTEN. Concomitant activation of PTEN, AR, and Runx factors occurs at early stages. At late stages, PTEN and AR are downregulated, while Runx1 and Runx2 remain elevated. Loss of Runx-targeting microRNAs, miR-23b-5p, miR-139-5p, miR-205-5p, miR-221-3p, miR-375-3p, miR-382-5p, and miR-384-5p, contribute to aberrant Runx expression in prostate tumors. Our studies reveal a Runx/miRNA interaction axis centered on PTEN-PI3K-AKT signaling. This regulatory network translates to mechanistic understanding of prostate tumorigenesis that can be developed for diagnosis and directed therapy.

Rights and Permissions

Citation: Oncotarget. 2016 Oct 25;7(43):70462-70474. doi: 10.18632/oncotarget.11992. Link to article on publisher's site. All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.

DOI of Published Version

10.18632/oncotarget.11992

Related Resources

Link to Article in PubMed

Keywords

AR, PTEN, TRAMP, miRNA targeting Runx, prostate cancer progression

Journal Title

Oncotarget

PubMed ID

27634876

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

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